rs6480320

Variant names:

• chr10-68231911-G-A
• rs6480320
• NM_145178.4:c.-234C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_145178.4(ATOH7):​c.-234C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0444 in 211,474 control chromosomes in the GnomAD database, including 947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (928 hom., cov: 33)
  • Exomes 𝑓: 0.0054 (19 hom.)
• Consequence: ATOH7 NM_145178.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.633
• Publications: 6 publications found

Genes affected

ATOH7 (HGNC:13907): (atonal bHLH transcription factor 7) This intronless gene encodes a member of the basic helix-loop-helix family of transcription factors, with similarity to Drosophila atonal gene that controls photoreceptor development. Studies in mice suggest that this gene plays a central role in retinal ganglion cell and optic nerve formation. Mutations in this gene are associated with nonsyndromic congenital retinal nonattachment. [provided by RefSeq, Dec 2011]

ATOH7 Gene-Disease associations (from GenCC):

• persistent hyperplastic primary vitreous, autosomal recessive

  Inheritance: Unknown, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• persistent hyperplastic primary vitreous

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• anterior segment dysgenesis 7

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-68231911-G-A is Benign according to our data. Variant chr10-68231911-G-A is described in ClinVar as Benign. ClinVar VariationId is 1254659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145178.4. 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
	ATOH7	NM_145178.4	MANE Select	c.-234C>T		5_prime_UTR	Exon 1 of 1	NP_660161.1	Q8N100

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATOH7	ENST00000373673.5	TSL:6 MANE Select	c.-234C>T		5_prime_UTR	Exon 1 of 1	ENSP00000362777.3	Q8N100

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9056 AN: 152164 Hom.: 926 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.0464

GnomAD4 exome AF: 0.00536 AC: 317 AN: 59192 Hom.: 19 Cov.: 3 AF XY: 0.00456 AC XY: 138 AN XY: 30296

African (AFR) AF: 0.187 AC: 200 AN: 1072

American (AMR) AF: 0.0174 AC: 20 AN: 1148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1388

East Asian (EAS) AF: 0.00 AC: 0 AN: 3942

South Asian (SAS) AF: 0.00 AC: 0 AN: 384

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18848

Middle Eastern (MID) AF: 0.00909 AC: 2 AN: 220

European-Non Finnish (NFE) AF: 0.00146 AC: 43 AN: 29420

Other (OTH) AF: 0.0188 AC: 52 AN: 2770

GnomAD4 genome AF: 0.0596 AC: 9076 AN: 152282 Hom.: 928 Cov.: 33 AF XY: 0.0568 AC XY: 4230 AN XY: 74482

African (AFR) AF: 0.206 AC: 8557 AN: 41534

American (AMR) AF: 0.0229 AC: 350 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000941 AC: 64 AN: 68022

Other (OTH) AF: 0.0459 AC: 97 AN: 2114

Alfa AF: 0.0600 Hom.: 291

Bravo AF: 0.0688

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	14
DANN	Benign	0.63
PhyloP100		0.63
PromoterAI		-0.012	Neutral
Mutation Taster		=300/0	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: rs6480320; hg19: chr10-69991668;