chr10-86456645-G-A

Variant names:

• chr10-86456645-G-A
• rs7075426
• NM_015045.5:c.2657+2344C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

WAPL Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015045.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WAPL	NM_015045.5	MANE Select	c.2657+2344C>T		intron	N/A	NP_055860.1
	WAPL	NM_001318328.2		c.2639+2344C>T		intron	N/A	NP_001305257.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WAPL	ENST00000298767.10	TSL:1 MANE Select	c.2657+2344C>T		intron	N/A	ENSP00000298767.4
	WAPL	ENST00000372075.2	TSL:2	c.515+2344C>T		intron	N/A	ENSP00000361145.2

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

African (AFR) AF: 0.512 AC: 21186 AN: 41388

American (AMR) AF: 0.402 AC: 6146 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1550 AN: 3468

East Asian (EAS) AF: 0.694 AC: 3593 AN: 5176

South Asian (SAS) AF: 0.651 AC: 3134 AN: 4814

European-Finnish (FIN) AF: 0.505 AC: 5327 AN: 10544

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31114 AN: 67940

Other (OTH) AF: 0.462 AC: 975 AN: 2110

Alfa AF: 0.477 Hom.: 2880

Bravo AF: 0.474

Asia WGS AF: 0.639 AC: 2219 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.0
DANN	Benign	0.69
PhyloP100		-0.023
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: rs7075426; hg19: chr10-88216402;