4-70659795-A-G

Variant names:

• chr4-70659795-A-G
• rs6829524
• NM_144646.4:c.188+2297T>C

Variant summary

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

The NM_144646.4(JCHAIN):​c.188+2297T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 152,072 control chromosomes in the GnomAD database, including 114 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 0.022 (114 hom., cov: 30)
• Consequence: JCHAIN NM_144646.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.317
• Publications: 1 publications found

Genes affected

JCHAIN (HGNC:5713): (joining chain of multimeric IgA and IgM) Enables IgA binding activity and protein homodimerization activity. Contributes to several functions, including immunoglobulin receptor binding activity; peptidoglycan binding activity; and phosphatidylcholine binding activity. Involved in several processes, including defense response to other organism; glomerular filtration; and positive regulation of respiratory burst. Located in extracellular space. Part of monomeric IgA immunoglobulin complex; pentameric IgM immunoglobulin complex; and secretory dimeric IgA immunoglobulin complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286848 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JCHAIN	NM_144646.4	c.188+2297T>C		intron_variant	Intron 2 of 3	ENST00000254801.9	NP_653247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JCHAIN	ENST00000254801.9	c.188+2297T>C		intron_variant	Intron 2 of 3	1	NM_144646.4	ENSP00000254801.4

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3384 AN: 151952 Hom.: 112 Cov.: 30

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.000568

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00140

Gnomad OTH AF: 0.0163

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

GnomAD4 genome AF: 0.0224 AC: 3400 AN: 152072 Hom.: 114 Cov.: 30 AF XY: 0.0213 AC XY: 1584 AN XY: 74344

African (AFR) AF: 0.0718 AC: 2981 AN: 41496

American (AMR) AF: 0.0118 AC: 180 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3466

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5162

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4824

European-Finnish (FIN) AF: 0.000568 AC: 6 AN: 10568

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00140 AC: 95 AN: 67986

Other (OTH) AF: 0.0161 AC: 34 AN: 2110

Alfa AF: 0.0157 Hom.: 8

Bravo AF: 0.0253

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.83
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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: rs6829524; hg19: chr4-71525512;