14-100582060-C-T

Position:

• chr14-100582060-C-T

Variant summary

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

The NM_001385089.1(BEGAIN):​c.42+5189G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,310 control chromosomes in the GnomAD database, including 55,627 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 0.85 (55627 hom., cov: 36)
• Consequence: BEGAIN NM_001385089.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

Genes affected

BEGAIN (HGNC:24163): (brain enriched guanylate kinase associated) Predicted to be involved in regulation of postsynaptic neurotransmitter receptor activity. Predicted to act upstream of or within evoked excitatory postsynaptic potential. Predicted to be located in dendrite; nucleus; and presynapse. Predicted to be active in glutamatergic synapse and postsynapse. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEGAIN	NM_001385089.1	c.42+5189G>A		intron_variant		ENST00000554140.3	NP_001372018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEGAIN	ENST00000554140.3	c.42+5189G>A		intron_variant		5	NM_001385089.1	ENSP00000451125.2

Frequencies

GnomAD3 genomes AF: 0.848 AC: 129054 AN: 152192 Hom.: 55579 Cov.: 36

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.860

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.827

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

GnomAD4 genome AF: 0.848 AC: 129152 AN: 152310 Hom.: 55627 Cov.: 36 AF XY: 0.840 AC XY: 62538 AN XY: 74470

Gnomad4 AFR AF: 0.922

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.849

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.847

Gnomad4 FIN AF: 0.844

Gnomad4 NFE AF: 0.873

Gnomad4 OTH AF: 0.820

Alfa AF: 0.833 Hom.: 8967

Bravo AF: 0.835

Asia WGS AF: 0.654 AC: 2277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10873519; hg19: chr14-101048397;