rs4951338

Variant names:

• chr1-204260924-A-G
• rs4951338
• NM_014935.5:c.524+382T>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.524+382T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 152,102 control chromosomes in the GnomAD database, including 28,713 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 0.61 (28713 hom., cov: 32)
• Consequence: PLEKHA6 NM_014935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.804 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA6	NM_014935.5	MANE Select	c.524+382T>C		intron	N/A	NP_055750.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA6	ENST00000272203.8	TSL:1 MANE Select	c.524+382T>C		intron	N/A	ENSP00000272203.2	Q9Y2H5
	PLEKHA6	ENST00000637508.1	TSL:5	c.524+382T>C		intron	N/A	ENSP00000490182.1	A0A1B0GUN5
	PLEKHA6	ENST00000943171.1		c.524+382T>C		intron	N/A	ENSP00000613230.1

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92726 AN: 151984 Hom.: 28675 Cov.: 32

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.610 AC: 92809 AN: 152102 Hom.: 28713 Cov.: 32 AF XY: 0.619 AC XY: 45989 AN XY: 74348

African (AFR) AF: 0.638 AC: 26465 AN: 41472

American (AMR) AF: 0.659 AC: 10077 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2003 AN: 3466

East Asian (EAS) AF: 0.825 AC: 4271 AN: 5176

South Asian (SAS) AF: 0.537 AC: 2585 AN: 4816

European-Finnish (FIN) AF: 0.720 AC: 7627 AN: 10588

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.557 AC: 37894 AN: 67986

Other (OTH) AF: 0.585 AC: 1232 AN: 2106

Alfa AF: 0.576 Hom.: 113540

Bravo AF: 0.611

Asia WGS AF: 0.680 AC: 2367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.6
DANN	Benign	0.74
PhyloP100		0.064
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: rs4951338; hg19: chr1-204230052;