rs7592040

chr2-26518683-G-Achr2-26518683-G-T

Variant summary

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

The NM_194248.3(OTOF):c.327+327C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,232 control chromosomes in the GnomAD database, including 6,029 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 0.25 (6029 hom., cov: 35)
• Consequence: OTOF NM_194248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.875

Genes affected

OTOF (HGNC:8515): (otoferlin) Mutations in this gene are a cause of neurosensory nonsyndromic recessive deafness, DFNB9. The short form of the encoded protein has 3 C2 domains, a single carboxy-terminal transmembrane domain found also in the C. elegans spermatogenesis factor FER-1 and human dysferlin, while the long form has 6 C2 domains. The homology suggests that this protein may be involved in vesicle membrane fusion. Several transcript variants encoding multiple isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOF	NM_194248.3	c.327+327C>T		intron_variant		ENST00000272371.7
OTOF	NM_001287489.2	c.327+327C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTOF	ENST00000272371.7	c.327+327C>T		intron_variant		1	NM_194248.3	A1
OTOF	ENST00000403946.7	c.327+327C>T		intron_variant		5		P4

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38756 AN: 152114 Hom.: 6021 Cov.: 35

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.221

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.255 AC: 38772 AN: 152232 Hom.: 6029 Cov.: 35 AF XY: 0.265 AC XY: 19723 AN XY: 74430

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.562

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.228

Alfa AF: 0.270 Hom.: 9043

Bravo AF: 0.233

Asia WGS AF: 0.468 AC: 1628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	9.4
Dann	Benign	0.69

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: rs7592040; hg19: chr2-26741551;