rs6746541

Positions:

• chr2-85774505-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032827.7(ATOH8):​c.960+10323T>C variant causes a intron 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 NM_032827.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ATOH8	NM_032827.7	c.960+10323T>C		intron_variant		ENST00000306279.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATOH8	ENST00000306279.4	c.960+10323T>C		intron_variant		1	NM_032827.7	P1
ATOH8	ENST00000463422.5	n.2391T>C		non_coding_transcript_exon_variant	3/3	1
ATOH8	ENST00000469442.5	n.711+10323T>C		intron_variant, non_coding_transcript_variant		2
ATOH8	ENST00000473116.1	n.347-5868T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR exome AF: 0.468

Gnomad4 AMR exome AF: 0.520

Gnomad4 ASJ exome AF: 0.460

Gnomad4 EAS exome AF: 0.708

Gnomad4 SAS exome AF: 0.301

Gnomad4 FIN exome AF: 0.319

Gnomad4 NFE exome AF: 0.346

Gnomad4 OTH exome AF: 0.388

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

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.448

Alfa AF: 0.387 Hom.: 15044

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

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

Other links and lift over

dbSNP: rs6746541; hg19: chr2-86001628;