rs7534537

Positions:

• chr1-204305391-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.-94-30582A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0537 in 152,264 control chromosomes in the GnomAD database, including 350 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 0.054 (350 hom., cov: 32)
• Consequence: PLEKHA6 NM_014935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHA6	NM_014935.5	c.-94-30582A>G		intron_variant		ENST00000272203.8	NP_055750.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHA6	ENST00000272203.8	c.-94-30582A>G		intron_variant		1	NM_014935.5	ENSP00000272203.2
PLEKHA6	ENST00000637508.1	c.-95+1946A>G		intron_variant		5		ENSP00000490182.1
PLEKHA6	ENST00000414478.1	c.-94-30582A>G		intron_variant		5		ENSP00000402046.1
PLEKHA6	ENST00000564627.2	c.219-30582A>G		intron_variant		3		ENSP00000490720.2

Frequencies

GnomAD3 genomes AF: 0.0536 AC: 8161 AN: 152146 Hom.: 348 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0363

Gnomad ASJ AF: 0.0686

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.00753

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.0557

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

GnomAD4 genome AF: 0.0537 AC: 8170 AN: 152264 Hom.: 350 Cov.: 32 AF XY: 0.0523 AC XY: 3892 AN XY: 74460

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.0361

Gnomad4 ASJ AF: 0.0686

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0315

Gnomad4 FIN AF: 0.00753

Gnomad4 NFE AF: 0.0263

Gnomad4 OTH AF: 0.0547

Alfa AF: 0.0506 Hom.: 48

Bravo AF: 0.0582

Asia WGS AF: 0.0170 AC: 61 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.46
DANN	Benign	0.77

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: rs7534537; hg19: chr1-204274519;