rs7075426

Positions:

• chr10-86456645-G-A
• chr10-86456645-G-C

Variant summary

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

The NM_015045.5(WAPL):​c.2657+2344C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,934 control chromosomes in the GnomAD database, including 18,173 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 0.48 (18173 hom., cov: 31)
• Consequence: WAPL NM_015045.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

Genes affected

WAPL (HGNC:23293): (WAPL cohesin release factor) Involved in several processes, including negative regulation of DNA replication; negative regulation of chromatin binding activity; and regulation of sister chromatid cohesion. Located in several cellular components, including Golgi apparatus; intercellular bridge; and microtubule cytoskeleton. [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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WAPL	NM_015045.5	c.2657+2344C>T		intron_variant		ENST00000298767.10
WAPL	NM_001318328.2	c.2639+2344C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WAPL	ENST00000298767.10	c.2657+2344C>T		intron_variant		1	NM_015045.5	P1
WAPL	ENST00000372075.2	c.515+2344C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73588 AN: 151816 Hom.: 18160 Cov.: 31

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.485 AC: 73639 AN: 151934 Hom.: 18173 Cov.: 31 AF XY: 0.492 AC XY: 36506 AN XY: 74272

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.462

Alfa AF: 0.476 Hom.: 2778

Bravo AF: 0.474

Asia WGS AF: 0.639 AC: 2219 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.0
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: rs7075426; hg19: chr10-88216402;