Genetic Variant NM_001391957.1:c.2118G>C (chr1-15341876-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001391957.1(FHAD1):c.2118G>C(p.Thr706Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000355 in 1,551,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

FHAD1
NM_001391957.1 synonymous

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0180

Publications

2 publications found

Variant links:

Genes affected

FHAD1 (HGNC:29408): (forkhead associated phosphopeptide binding domain 1)

FHAD1 links:

FHAD1-AS1 (HGNC:41241): (FHAD1 antisense RNA 1)

FHAD1-AS1 links:

EFHD2-AS1 (HGNC:55801): (EFHD2 antisense RNA 1)

EFHD2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027803093).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001391957.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FHAD1	NM_001391957.1	MANE Select	c.2118G>C	p.Thr706Thr	synonymous	Exon 16 of 34	NP_001378886.1	A0A804HIA4
FHAD1	NM_052929.2		c.2047G>C	p.Gly683Arg	missense	Exon 15 of 31	NP_443161.1	B1AJZ9-1
FHAD1-AS1	NR_148918.1		n.108+1900C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FHAD1	ENST00000688493.1	MANE Select	c.2118G>C	p.Thr706Thr	synonymous	Exon 16 of 34	ENSP00000509124.1	A0A804HIA4
FHAD1	ENST00000471347.5	TSL:1	n.584G>C		non_coding_transcript_exon	Exon 5 of 24
FHAD1	ENST00000358897.8	TSL:5	c.2047G>C	p.Gly683Arg	missense	Exon 15 of 31	ENSP00000351770.4	B1AJZ9-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000832

AC:

AN:

156170

AF XY:

0.000133

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000472

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000331

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000365

AC:

AN:

1399138

Hom.:

Cov.:

AF XY:

0.0000493

AC XY:

AN XY:

690074

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31584

American (AMR)

AF:

0.00

AC:

AN:

35650

Ashkenazi Jewish (ASJ)

AF:

0.000636

AC:

AN:

25164

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35734

South Asian (SAS)

AF:

0.000227

AC:

AN:

79186

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.00000927

AC:

AN:

1078836

Other (OTH)

AF:

0.000103

AC:

AN:

57998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68046

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

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:

0.00000677

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.000119

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.50

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.00082

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.44

M_CAP

Benign

0.014

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.90

PhyloP100

-0.018

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.54

REVEL

Benign

0.015

Sift

Benign

0.26

Sift4G

Benign

0.59

Polyphen

0.12

Vest4

0.16

MutPred

0.10

Loss of loop (P = 0.0203)

MVP

0.076

ClinPred

0.017

GERP RS

1.4

PromoterAI

-0.0055

Neutral

(source)

Varity_R

0.074

gMVP

0.16

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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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