rs4951353

Variant names:

• chr1-204286720-A-G
• rs4951353
• NM_014935.5:c.-94-11911T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014935.5(PLEKHA6):​c.-94-11911T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 152,044 control chromosomes in the GnomAD database, including 25,498 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 0.57 (25498 hom., cov: 31)
• Consequence: PLEKHA6 NM_014935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 3 publications found

Genes affected

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

PLEKHA6 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014935.5. 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
	PLEKHA6	NM_014935.5	MANE Select	c.-94-11911T>C		intron	N/A	NP_055750.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA6	ENST00000272203.8	TSL:1 MANE Select	c.-94-11911T>C		intron	N/A	ENSP00000272203.2
	PLEKHA6	ENST00000637508.1	TSL:5	c.-94-11911T>C		intron	N/A	ENSP00000490182.1
	PLEKHA6	ENST00000414478.1	TSL:5	c.-94-11911T>C		intron	N/A	ENSP00000402046.1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87004 AN: 151926 Hom.: 25461 Cov.: 31

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.573 AC: 87097 AN: 152044 Hom.: 25498 Cov.: 31 AF XY: 0.572 AC XY: 42472 AN XY: 74314

African (AFR) AF: 0.698 AC: 28963 AN: 41472

American (AMR) AF: 0.570 AC: 8720 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1975 AN: 3472

East Asian (EAS) AF: 0.585 AC: 3013 AN: 5150

South Asian (SAS) AF: 0.433 AC: 2082 AN: 4810

European-Finnish (FIN) AF: 0.548 AC: 5794 AN: 10578

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34758 AN: 67954

Other (OTH) AF: 0.572 AC: 1206 AN: 2110

Alfa AF: 0.536 Hom.: 34681

Bravo AF: 0.583

Asia WGS AF: 0.570 AC: 1981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.3
DANN	Benign	0.83
PhyloP100		1.1
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: rs4951353; hg19: chr1-204255848;