rs6746541

Variant names:

• chr2-85774505-T-C
• rs6746541
• ENST00000463422.5:n.2391T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000463422.5(ATOH8):​n.2391T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 985,176 control chromosomes in the GnomAD database, including 65,262 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (13207 hom., cov: 33)
  • Exomes 𝑓: 0.35 (52055 hom.)
• Consequence: ATOH8 ENST00000463422.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 7 publications found

Genes affected

ATOH8 (HGNC:24126): (atonal bHLH transcription factor 8) Enables DNA-binding transcription factor activity and E-box binding activity. Involved in several processes, including SMAD protein signal transduction; positive regulation of endothelial cell differentiation; and regulation of gene expression. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATOH8	NM_032827.7	c.960+10323T>C		intron_variant	Intron 2 of 2	ENST00000306279.4	NP_116216.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATOH8	ENST00000306279.4	c.960+10323T>C		intron_variant	Intron 2 of 2	1	NM_032827.7	ENSP00000304676.3

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61944 AN: 151954 Hom.: 13202 Cov.: 33

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.448

GnomAD4 exome AF: 0.352 AC: 292882 AN: 833104 Hom.: 52055 Cov.: 54 AF XY: 0.352 AC XY: 135245 AN XY: 384716

African (AFR) AF: 0.468 AC: 7395 AN: 15790

American (AMR) AF: 0.520 AC: 512 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 2369 AN: 5152

East Asian (EAS) AF: 0.708 AC: 2573 AN: 3632

South Asian (SAS) AF: 0.301 AC: 4951 AN: 16458

European-Finnish (FIN) AF: 0.319 AC: 88 AN: 276

Middle Eastern (MID) AF: 0.458 AC: 742 AN: 1620

European-Non Finnish (NFE) AF: 0.346 AC: 263649 AN: 761894

Other (OTH) AF: 0.388 AC: 10603 AN: 27298

GnomAD4 genome AF: 0.408 AC: 61978 AN: 152072 Hom.: 13207 Cov.: 33 AF XY: 0.406 AC XY: 30214 AN XY: 74348

African (AFR) AF: 0.453 AC: 18758 AN: 41450

American (AMR) AF: 0.497 AC: 7603 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1650 AN: 3470

East Asian (EAS) AF: 0.701 AC: 3620 AN: 5166

South Asian (SAS) AF: 0.322 AC: 1554 AN: 4830

European-Finnish (FIN) AF: 0.302 AC: 3195 AN: 10580

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24241 AN: 67970

Other (OTH) AF: 0.448 AC: 946 AN: 2110

Alfa AF: 0.390 Hom.: 27913

Bravo AF: 0.429

Asia WGS AF: 0.492 AC: 1714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.8
DANN	Benign	0.72
PhyloP100		-0.091
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6746541; hg19: chr2-86001628;