14-100538218-G-A

Variant names:

• chr14-100538218-G-A
• rs112914069
• NM_001385089.1:c.1590C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001385089.1(BEGAIN):​c.1590C>T​(p.Pro530Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00033 in 1,565,980 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: BEGAIN NM_001385089.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.191
• 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]

LOC124903382 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 14-100538218-G-A is Benign according to our data. Variant chr14-100538218-G-A is described in ClinVar as Benign. ClinVar VariationId is 707933.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.191 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385089.1. 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
	BEGAIN	NM_001385089.1	MANE Select	c.1590C>T	p.Pro530Pro	synonymous	Exon 7 of 7	NP_001372018.1	G3V3A2
	BEGAIN	NM_001385085.1		c.1680C>T	p.Pro560Pro	synonymous	Exon 8 of 8	NP_001372014.1
	BEGAIN	NM_001385086.1		c.1662C>T	p.Pro554Pro	synonymous	Exon 8 of 8	NP_001372015.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BEGAIN	ENST00000554140.3	TSL:5 MANE Select	c.1590C>T	p.Pro530Pro	synonymous	Exon 7 of 7	ENSP00000451125.2	G3V3A2
	BEGAIN	ENST00000355173.7	TSL:1	c.1533C>T	p.Pro511Pro	synonymous	Exon 7 of 7	ENSP00000347301.2	Q9BUH8
	BEGAIN	ENST00000557378.6	TSL:1	c.1533C>T	p.Pro511Pro	synonymous	Exon 6 of 6	ENSP00000450722.2	Q9BUH8

Frequencies

GnomAD3 genomes AF: 0.00183 AC: 278 AN: 151986 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00599

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.000546 AC: 96 AN: 175814 AF XY: 0.000488

Gnomad AFR exome AF: 0.00764

Gnomad AMR exome AF: 0.000485

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000133

Gnomad OTH exome AF: 0.000659

GnomAD4 exome AF: 0.000170 AC: 240 AN: 1413876 Hom.: 1 Cov.: 31 AF XY: 0.000145 AC XY: 102 AN XY: 701192

African (AFR) AF: 0.00554 AC: 178 AN: 32106

American (AMR) AF: 0.000702 AC: 28 AN: 39880

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24524

East Asian (EAS) AF: 0.00 AC: 0 AN: 38210

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5542

European-Non Finnish (NFE) AF: 0.00000823 AC: 9 AN: 1094038

Other (OTH) AF: 0.000410 AC: 24 AN: 58572

GnomAD4 genome AF: 0.00182 AC: 277 AN: 152104 Hom.: 0 Cov.: 33 AF XY: 0.00164 AC XY: 122 AN XY: 74352

African (AFR) AF: 0.00595 AC: 247 AN: 41506

American (AMR) AF: 0.00157 AC: 24 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67948

Other (OTH) AF: 0.00190 AC: 4 AN: 2108

Alfa AF: 0.000859 Hom.: 0

Bravo AF: 0.00228

Asia WGS AF: 0.000289 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.85
PhyloP100		-0.19

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: rs112914069; hg19: chr14-101004555;