chr14-105766769-G-A

Variant names:

• chr14-105766769-G-A
• rs34295723
• ENST00000641136.1:c.1255-772C>T

Variant summary

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

The ENST00000641136.1(IGHG3):​c.1255-772C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 139,360 control chromosomes in the GnomAD database, including 20,164 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 0.51 (20164 hom., cov: 22)
• Consequence: IGHG3 ENST00000641136.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.453
• Publications: 1 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGH		n.105766769G>A		intragenic_variant
IGHG3	unassigned_transcript_2476	c.1255-772C>T		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGHG3	ENST00000641136.1	c.1255-772C>T		intron_variant	Intron 8 of 8			ENSP00000492969.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 71247 AN: 139242 Hom.: 20169 Cov.: 22

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.777

Gnomad EAS AF: 0.0877

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.641

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.511 AC: 71258 AN: 139360 Hom.: 20164 Cov.: 22 AF XY: 0.502 AC XY: 33914 AN XY: 67622

African (AFR) AF: 0.260 AC: 9915 AN: 38088

American (AMR) AF: 0.420 AC: 5738 AN: 13658

Ashkenazi Jewish (ASJ) AF: 0.777 AC: 2539 AN: 3266

East Asian (EAS) AF: 0.0882 AC: 384 AN: 4356

South Asian (SAS) AF: 0.487 AC: 1899 AN: 3902

European-Finnish (FIN) AF: 0.576 AC: 5499 AN: 9546

Middle Eastern (MID) AF: 0.633 AC: 114 AN: 180

European-Non Finnish (NFE) AF: 0.685 AC: 43574 AN: 63652

Other (OTH) AF: 0.528 AC: 995 AN: 1886

Alfa AF: 0.579 Hom.: 2800

Asia WGS AF: 0.305 AC: 1057 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.2
DANN	Benign	0.40
PhyloP100		0.45

Splicing

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

Other links and lift over

dbSNP: rs34295723; hg19: chr14-106233106; COSMIC: COSV66653132;