rs17334002

Positions:

• chr1-204336981-T-C

Variant summary

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

The NM_014935.5(PLEKHA6):​c.-95+22713A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,232 control chromosomes in the GnomAD database, including 3,382 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 0.19 (3382 hom., cov: 32)
• Consequence: PLEKHA6 NM_014935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHA6	NM_014935.5	c.-95+22713A>G		intron_variant		ENST00000272203.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHA6	ENST00000272203.8	c.-95+22713A>G		intron_variant		1	NM_014935.5	P2
PLEKHA6	ENST00000414478.1	c.-95+22713A>G		intron_variant		5
PLEKHA6	ENST00000564627.2	c.218+30818A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29409 AN: 152114 Hom.: 3381 Cov.: 32

Gnomad AFR AF: 0.0791

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.193 AC: 29415 AN: 152232 Hom.: 3382 Cov.: 32 AF XY: 0.195 AC XY: 14511 AN XY: 74426

Gnomad4 AFR AF: 0.0789

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.194

Alfa AF: 0.240 Hom.: 6111

Bravo AF: 0.176

Asia WGS AF: 0.184 AC: 639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.20
DANN	Benign	0.76

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: rs17334002; hg19: chr1-204306109;