dbSNP rs545441558: BHLHA9:p.Thr11Thr (chr17-1270596-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001164405.2(BHLHA9):c.33G>A(p.Thr11Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000338 in 1,282,314 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

BHLHA9
NM_001164405.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.160

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

mesoaxial synostotic syndactyly with phalangeal reduction
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
tibial aplasia-ectrodactyly syndrome
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
Camptosynpolydactyly, complex
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
split-hand/foot malformation with long bone deficiency 1
Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

BHLHA9 links:

ENSG00000300095 (HGNC:):

ENSG00000300095 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 17-1270596-G-A is Benign according to our data. Variant chr17-1270596-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 730614.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.16 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164405.2. 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
	BHLHA9	NM_001164405.2	MANE Select	c.33G>A	p.Thr11Thr	synonymous	Exon 1 of 1	NP_001157877.1	Q7RTU4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BHLHA9	ENST00000391429.2	TSL:6 MANE Select	c.33G>A	p.Thr11Thr	synonymous	Exon 1 of 1	ENSP00000375248.1	Q7RTU4
ENSG00000300095	ENST00000768751.1		n.-92C>T		upstream_gene	N/A
ENSG00000300095	ENST00000768752.1		n.-95C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.00173

AC:

263

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00613

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00

AC:

AN:

400

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000142

AC:

161

AN:

1130030

Hom.:

Cov.:

AF XY:

0.000137

AC XY:

AN XY:

538662

show subpopulations

African (AFR)

AF:

0.00537

AC:

124

AN:

23094

American (AMR)

AF:

0.000234

AC:

AN:

8538

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15260

East Asian (EAS)

AF:

0.00

AC:

AN:

26734

South Asian (SAS)

AF:

0.00

AC:

AN:

30608

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24396

Middle Eastern (MID)

AF:

0.000299

AC:

AN:

3340

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

951840

Other (OTH)

AF:

0.000606

AC:

AN:

46220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

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:

0.00179

AC:

273

AN:

152284

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

140

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.00635

AC:

264

AN:

41570

American (AMR)

AF:

0.000457

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68004

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00192

Hom.:

Bravo

AF:

0.00182

Asia WGS

AF:

0.00144

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

BHLHA9-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.7

(source)

DANN

Benign

0.85

PhyloP100

-0.16

PromoterAI

-0.0098

Neutral

(source)

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

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