17-1270679-C-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001164405.2(BHLHA9):c.116C>A(p.Ala39Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000881 in 1,321,460 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 8 hom., cov: 33)

Exomes 𝑓: 0.00042 ( 6 hom. )

Consequence

BHLHA9
NM_001164405.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.237

Variant links:

Genes affected

BHLHA9 (HGNC:35126): (basic helix-loop-helix family member a9) This gene is a member of the basic helix-loop-helix family. The encoded protein is a transcription factor involved in limb development. Mutations in this gene have been associated with mesoaxial synostotic syndactyly Malik-Percin type (MSSD). Copy number variation of a locus containing this gene has been linked to a form of split-hand/foot malformation with long bone deficiency (SHFLD3). [provided by RefSeq, Mar 2015]

BHLHA9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004467815).

BP6

Variant 17-1270679-C-A is Benign according to our data. Variant chr17-1270679-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 501415.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-1270679-C-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000416 (486/1169298) while in subpopulation AFR AF= 0.0175 (408/23326). AF 95% confidence interval is 0.0161. There are 6 homozygotes in gnomad4_exome. There are 195 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BHLHA9	NM_001164405.2 link	c.116C>A	p.Ala39Glu	missense_variant	Exon 1 of 1	ENST00000391429.2	NP_001157877.1	Q7RTU4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BHLHA9	ENST00000391429.2 link	c.116C>A	p.Ala39Glu	missense_variant	Exon 1 of 1	6	NM_001164405.2	ENSP00000375248.1		Q7RTU4

Frequencies

GnomAD3 genomes

AF:

0.00443

AC:

673

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00382

GnomAD4 exome

AF:

0.000416

AC:

486

AN:

1169298

Hom.:

Cov.:

AF XY:

0.000345

AC XY:

195

AN XY:

564690

show subpopulations

Gnomad4 AFR exome

AF:

0.0175

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000205

Gnomad4 OTH exome

AF:

0.00132

GnomAD4 genome

AF:

0.00446

AC:

678

AN:

152162

Hom.:

Cov.:

AF XY:

0.00394

AC XY:

293

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0156

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00319

Hom.:

Bravo

AF:

0.00501

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Apr 11, 2017

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Benign

5.5

DANN

Benign

0.72

DEOGEN2

Benign

0.0030

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.24

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.0045

MetaSVM

Benign

-0.43

MutationAssessor

Benign

-1.1

PrimateAI

Uncertain

0.67

PROVEAN

Benign

1.4

REVEL

Benign

0.19

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.064

MVP

0.24

ClinPred

0.029

GERP RS

1.3

Varity_R

0.050

gMVP

0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over