Variant chr10-122416936-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001001974.4(PLEKHA1):c.612+934G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 153,858 control chromosomes in the GnomAD database, including 18,122 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 0.48 ( 17813 hom., cov: 29)

Exomes 𝑓: 0.49 ( 309 hom. )

Consequence

PLEKHA1
NM_001001974.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.428

Variant links:

Genes affected

PLEKHA1 (HGNC:14335): (pleckstrin homology domain containing A1) This gene encodes a pleckstrin homology domain-containing adapter protein. The encoded protein is localized to the plasma membrane where it specifically binds phosphatidylinositol 3,4-bisphosphate. This protein may be involved in the formation of signaling complexes in the plasma membrane. Polymorphisms in this gene are associated with age-related macular degeneration. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 5.[provided by RefSeq, Sep 2010]

PLEKHA1 links:

MIR3941 (HGNC:38949): (microRNA 3941) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR3941 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHA1	NM_001001974.4 linkuse as main transcript	c.612+934G>A		intron_variant		ENST00000368990.8
MIR3941	NR_037506.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHA1	ENST00000368990.8 linkuse as main transcript	c.612+934G>A		intron_variant		1	NM_001001974.4	P3	Q9HB21-1
MIR3941	ENST00000582572.1 linkuse as main transcript			upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.476

AC:

72057

AN:

151252

Hom.:

17791

Cov.:

show subpopulations

Gnomad AFR

AF:

0.374

Gnomad AMI

AF:

0.525

Gnomad AMR

AF:

0.555

Gnomad ASJ

AF:

0.433

Gnomad EAS

AF:

0.625

Gnomad SAS

AF:

0.559

Gnomad FIN

AF:

0.634

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.482

Gnomad OTH

AF:

0.461

GnomAD3 exomes

AF:

0.470

AC:

2704

AN:

5750

Hom.:

630

AF XY:

0.467

AC XY:

1263

AN XY:

2704

show subpopulations

Gnomad AFR exome

AF:

0.360

Gnomad AMR exome

AF:

0.538

Gnomad ASJ exome

AF:

0.489

Gnomad EAS exome

AF:

0.583

Gnomad SAS exome

AF:

0.519

Gnomad NFE exome

AF:

0.472

Gnomad OTH exome

AF:

0.515

GnomAD4 exome

AF:

0.489

AC:

1217

AN:

2488

Hom.:

309

Cov.:

AF XY:

0.500

AC XY:

641

AN XY:

1282

show subpopulations

Gnomad4 AFR exome

AF:

0.300

Gnomad4 AMR exome

AF:

0.833

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.478

Gnomad4 FIN exome

AF:

0.602

Gnomad4 NFE exome

AF:

0.533

Gnomad4 OTH exome

AF:

0.417

GnomAD4 genome

AF:

0.476

AC:

72118

AN:

151370

Hom.:

17813

Cov.:

AF XY:

0.488

AC XY:

36093

AN XY:

73914

show subpopulations

Gnomad4 AFR

AF:

0.374

Gnomad4 AMR

AF:

0.556

Gnomad4 ASJ

AF:

0.433

Gnomad4 EAS

AF:

0.625

Gnomad4 SAS

AF:

0.560

Gnomad4 FIN

AF:

0.634

Gnomad4 NFE

AF:

0.482

Gnomad4 OTH

AF:

0.464

Alfa

AF:

0.498

Hom.:

2421

Bravo

AF:

0.469

Asia WGS

AF:

0.577

AC:

2004

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.5

DANN

Benign

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over