rs3981351

Positions:

• chr10-113755361-G-A
• chr10-113755361-G-T

Variant summary

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

The NM_001395068.1(PLEKHS1):​c.28+56G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,578,962 control chromosomes in the GnomAD database, including 440,173 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 0.73 (40357 hom., cov: 31)
  • Exomes 𝑓: 0.75 (399816 hom.)
• Consequence: PLEKHS1 NM_001395068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490

Genes affected

PLEKHS1 (HGNC:26285): (pleckstrin homology domain containing S1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHS1	NM_001395068.1	c.28+56G>A		intron_variant		ENST00000694986.1	NP_001381997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHS1	ENST00000694986.1	c.28+56G>A		intron_variant			NM_001395068.1	ENSP00000511629	P1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110450 AN: 151880 Hom.: 40322 Cov.: 31

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.750

GnomAD4 exome AF: 0.747 AC: 1066388 AN: 1426966 Hom.: 399816 Cov.: 41 AF XY: 0.749 AC XY: 530413 AN XY: 708012

Gnomad4 AFR exome AF: 0.681

Gnomad4 AMR exome AF: 0.729

Gnomad4 ASJ exome AF: 0.802

Gnomad4 EAS exome AF: 0.565

Gnomad4 SAS exome AF: 0.776

Gnomad4 FIN exome AF: 0.744

Gnomad4 NFE exome AF: 0.753

Gnomad4 OTH exome AF: 0.752

GnomAD4 genome AF: 0.727 AC: 110536 AN: 151996 Hom.: 40357 Cov.: 31 AF XY: 0.728 AC XY: 54078 AN XY: 74290

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.753

Gnomad4 ASJ AF: 0.813

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.743

Gnomad4 NFE AF: 0.750

Gnomad4 OTH AF: 0.749

Alfa AF: 0.748 Hom.: 43141

Bravo AF: 0.726

Asia WGS AF: 0.710 AC: 2470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.60

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: rs3981351; hg19: chr10-115515120;