rs144830740

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003923.3(FOXH1):c.338G>C(p.Ser113Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00576 in 1,606,692 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0059 ( 37 hom. )

Consequence

FOXH1
NM_003923.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.0440

Publications

7 publications found

Variant links:

Genes affected

FOXH1 (HGNC:3814): (forkhead box H1) FOXH1 encodes a human homolog of Xenopus forkhead activin signal transducer-1. FOXH1 protein binds SMAD2 and activates an activin response element via binding the DNA motif TGT(G/T)(T/G)ATT. [provided by RefSeq, Jul 2008]

FOXH1 Gene-Disease associations (from GenCC):

congenital heart malformation
Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine

FOXH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009800464).

BP6

Variant 8-144474998-C-G is Benign according to our data. Variant chr8-144474998-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 94385.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0045 (685/152338) while in subpopulation NFE AF = 0.00845 (575/68020). AF 95% confidence interval is 0.00788. There are 1 homozygotes in GnomAd4. There are 280 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 37 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003923.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXH1	NM_003923.3	MANE Select	c.338G>C	p.Ser113Thr	missense	Exon 3 of 3	NP_003914.1	O75593

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOXH1	ENST00000377317.5	TSL:1 MANE Select	c.338G>C	p.Ser113Thr	missense	Exon 3 of 3	ENSP00000366534.4	O75593
FOXH1	ENST00000935088.1		c.329G>C	p.Ser110Thr	missense	Exon 3 of 3	ENSP00000605147.1
FOXH1	ENST00000935090.1		c.326G>C	p.Ser109Thr	missense	Exon 3 of 3	ENSP00000605149.1

Frequencies

GnomAD3 genomes

AF:

0.00450

AC:

685

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00845

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00395

AC:

911

AN:

230876

AF XY:

0.00403

show subpopulations

Gnomad AFR exome

AF:

0.000802

Gnomad AMR exome

AF:

0.000539

Gnomad ASJ exome

AF:

0.00711

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00133

Gnomad NFE exome

AF:

0.00753

Gnomad OTH exome

AF:

0.00297

GnomAD4 exome

AF:

0.00589

AC:

8563

AN:

1454354

Hom.:

Cov.:

AF XY:

0.00590

AC XY:

4266

AN XY:

722986

show subpopulations

African (AFR)

AF:

0.000991

AC:

AN:

33308

American (AMR)

AF:

0.000658

AC:

AN:

44058

Ashkenazi Jewish (ASJ)

AF:

0.00562

AC:

146

AN:

25964

East Asian (EAS)

AF:

0.00

AC:

AN:

39342

South Asian (SAS)

AF:

0.0000235

AC:

AN:

85196

European-Finnish (FIN)

AF:

0.00217

AC:

111

AN:

51204

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00723

AC:

8018

AN:

1109468

Other (OTH)

AF:

0.00371

AC:

223

AN:

60062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

573

1147

1720

2294

2867

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

260

520

780

1040

1300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00450

AC:

685

AN:

152338

Hom.:

Cov.:

AF XY:

0.00376

AC XY:

280

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.000818

AC:

AN:

41576

American (AMR)

AF:

0.00105

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00188

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00845

AC:

575

AN:

68020

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

104

138

173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00697

Hom.:

Bravo

AF:

0.00396

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.000684

AC:

ESP6500EA

AF:

0.00666

AC:

ExAC

AF:

0.00424

AC:

512

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

not specified (4)

Holoprosencephaly sequence (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Uncertain

0.11

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

Eigen

Benign

0.049

Eigen_PC

Benign

0.024

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.64

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.0098

MetaSVM

Uncertain

0.46

MutationAssessor

Benign

1.0

PhyloP100

0.044

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.92

REVEL

Pathogenic

0.66

Sift

Benign

0.13

Sift4G

Benign

0.17

Polyphen

0.99

Vest4

0.26

MVP

0.93

MPC

0.10

ClinPred

0.029

GERP RS

3.4

Varity_R

0.11

gMVP

0.41

Mutation Taster

=73/27

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over