rs4248154

Positions:

• chr6-31034839-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001395414.1(MUC22):​c.5223C>T​(p.His1741=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,535,300 control chromosomes in the GnomAD database, including 27,879 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 0.17 (2470 hom., cov: 31)
  • Exomes 𝑓: 0.18 (25409 hom.)
• Consequence: MUC22 NM_001395414.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

Genes affected

MUC22 (HGNC:39755): (mucin 22) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-1.51 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC22	NM_001395414.1	c.5223C>T	p.His1741=	synonymous_variant	4/4	ENST00000561890.1
MUC22	NM_001318484.1	c.5232C>T	p.His1744=	synonymous_variant	5/5
MUC22	NM_001198815.1	c.5223C>T	p.His1741=	synonymous_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC22	ENST00000561890.1	c.5223C>T	p.His1741=	synonymous_variant	4/4	2	NM_001395414.1	P1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26139 AN: 151816 Hom.: 2461 Cov.: 31

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.154

GnomAD3 exomes AF: 0.200 AC: 25667 AN: 128446 Hom.: 2771 AF XY: 0.205 AC XY: 14442 AN XY: 70334

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.183

Gnomad ASJ exome AF: 0.144

Gnomad EAS exome AF: 0.270

Gnomad SAS exome AF: 0.273

Gnomad FIN exome AF: 0.188

Gnomad NFE exome AF: 0.182

Gnomad OTH exome AF: 0.188

GnomAD4 exome AF: 0.184 AC: 254769 AN: 1383364 Hom.: 25409 Cov.: 36 AF XY: 0.188 AC XY: 128160 AN XY: 682582

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.184

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.384

Gnomad4 SAS exome AF: 0.271

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.172 AC: 26157 AN: 151936 Hom.: 2470 Cov.: 31 AF XY: 0.176 AC XY: 13066 AN XY: 74280

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.154

Alfa AF: 0.184 Hom.: 4675

Bravo AF: 0.165

Asia WGS AF: 0.252 AC: 875 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.82
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs4248154; hg19: chr6-31002616;