14-100582060-C-T

Variant names:

• chr14-100582060-C-T
• rs10873519
• NM_001385089.1:c.42+5189G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BEGAIN	NM_001385089.1	c.42+5189G>A		intron_variant	Intron 1 of 6	ENST00000554140.3	NP_001372018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BEGAIN	ENST00000554140.3	c.42+5189G>A		intron_variant	Intron 1 of 6	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

African (AFR) AF: 0.922 AC: 38347 AN: 41574

American (AMR) AF: 0.684 AC: 10464 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2947 AN: 3472

East Asian (EAS) AF: 0.437 AC: 2267 AN: 5186

South Asian (SAS) AF: 0.847 AC: 4093 AN: 4832

European-Finnish (FIN) AF: 0.844 AC: 8957 AN: 10610

Middle Eastern (MID) AF: 0.873 AC: 255 AN: 292

European-Non Finnish (NFE) AF: 0.873 AC: 59411 AN: 68022

Other (OTH) AF: 0.820 AC: 1736 AN: 2116

Alfa AF: 0.848 Hom.: 17011

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
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs10873519; hg19: chr14-101048397;