rs3126209

Positions:

• chr1-204348495-C-T

Variant summary

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

The NM_014935.5(PLEKHA6):​c.-95+11199G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,174 control chromosomes in the GnomAD database, including 2,805 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 0.18 (2805 hom., cov: 32)
• Consequence: PLEKHA6 NM_014935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.53

Genes affected

PLEKHA6 (HGNC:17053): (pleckstrin homology domain containing A6)

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 (NFE) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHA6	NM_014935.5	c.-95+11199G>A		intron_variant		ENST00000272203.8	NP_055750.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHA6	ENST00000272203.8	c.-95+11199G>A		intron_variant		1	NM_014935.5	ENSP00000272203.2
PLEKHA6	ENST00000414478.1	c.-95+11199G>A		intron_variant		5		ENSP00000402046.1
PLEKHA6	ENST00000564627.2	c.218+19304G>A		intron_variant		3		ENSP00000490720.2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27533 AN: 152056 Hom.: 2807 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.181 AC: 27535 AN: 152174 Hom.: 2805 Cov.: 32 AF XY: 0.182 AC XY: 13508 AN XY: 74374

Gnomad4 AFR AF: 0.0999

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.193

Alfa AF: 0.192 Hom.: 391

Bravo AF: 0.170

Asia WGS AF: 0.170 AC: 590 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	0.019
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs3126209; hg19: chr1-204317623;