dbSNP rs12897751: IGHG3:c.1254+402C>G (chr14-105767411-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000641136.1(IGHG3):c.1254+402C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.44 ( 16205 hom., cov: 19)

Consequence

IGHG3
ENST00000641136.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.65

Publications

2 publications found

Variant links:

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]

IGHG3 links:

IGH (HGNC:5477):

IGH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGH		n.105767411G>C		intragenic_variant
IGHG3	unassigned_transcript_2476	c.1254+402C>G		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGHG3	ENST00000641136.1 link	c.1254+402C>G		intron_variant	Intron 8 of 8			ENSP00000492969.1		A0A9H4DHQ2

Frequencies

GnomAD3 genomes

AF:

0.440

AC:

56583

AN:

128662

Hom.:

16210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.711

Gnomad AMR

AF:

0.376

Gnomad ASJ

AF:

0.738

Gnomad EAS

AF:

0.0121

Gnomad SAS

AF:

0.403

Gnomad FIN

AF:

0.544

Gnomad MID

AF:

0.609

Gnomad NFE

AF:

0.659

Gnomad OTH

AF:

0.483

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

GnomAD4 genome

AF:

0.439

AC:

56574

AN:

128782

Hom.:

16205

Cov.:

AF XY:

0.429

AC XY:

26645

AN XY:

62136

show subpopulations

African (AFR)

AF:

0.105

AC:

3848

AN:

36770

American (AMR)

AF:

0.376

AC:

4607

AN:

12244

Ashkenazi Jewish (ASJ)

AF:

0.738

AC:

2231

AN:

3022

East Asian (EAS)

AF:

0.0121

AC:

AN:

4048

South Asian (SAS)

AF:

0.403

AC:

1317

AN:

3270

European-Finnish (FIN)

AF:

0.544

AC:

4500

AN:

8266

Middle Eastern (MID)

AF:

0.607

AC:

AN:

140

European-Non Finnish (NFE)

AF:

0.659

AC:

38544

AN:

58492

Other (OTH)

AF:

0.478

AC:

833

AN:

1742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

983

1966

2950

3933

4916

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.520

Hom.:

2472

Asia WGS

AF:

0.195

AC:

671

AN:

3420

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

2.4

(source)

DANN

Benign

0.19

PhyloP100

-3.6

Splicing

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

Publications

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rs12897751

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over