rs10136766

Variant names:

• chr14-105766248-A-G
• rs10136766
• ENST00000641136.1:c.1255-251T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000641136.1(IGHG3):​c.1255-251T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 142,862 control chromosomes in the GnomAD database, including 21,905 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 0.49 (21905 hom., cov: 32)
• Consequence: IGHG3 ENST00000641136.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.76
• Publications: 10 publications found

Genes affected

IGHG3 (HGNC:5527): (immunoglobulin heavy constant gamma 3 (G3m marker)) Predicted to enable antigen binding activity and immunoglobulin receptor binding activity. Involved in retina homeostasis. Located in blood microparticle and extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

IGH (HGNC:5477):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000641136.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGHG3	ENST00000641136.1		c.1255-251T>C		intron	N/A	ENSP00000492969.1	A0A9H4DHQ2

Frequencies

GnomAD3 genomes AF: 0.491 AC: 70067 AN: 142764 Hom.: 21913 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.490 AC: 70050 AN: 142862 Hom.: 21905 Cov.: 32 AF XY: 0.479 AC XY: 33378 AN XY: 69662

African (AFR) AF: 0.132 AC: 4756 AN: 35914

American (AMR) AF: 0.414 AC: 5950 AN: 14374

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2663 AN: 3430

East Asian (EAS) AF: 0.0166 AC: 74 AN: 4464

South Asian (SAS) AF: 0.455 AC: 1985 AN: 4366

European-Finnish (FIN) AF: 0.588 AC: 6076 AN: 10336

Middle Eastern (MID) AF: 0.668 AC: 139 AN: 208

European-Non Finnish (NFE) AF: 0.698 AC: 46693 AN: 66870

Other (OTH) AF: 0.517 AC: 1036 AN: 2002

Alfa AF: 0.546 Hom.: 2282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.17
PhyloP100		-3.8

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10136766;

hg19: chr14-106232585;

COSMIC: COSV66652363;