rs4713419

Positions:

• chr6-31025459-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395414.1(MUC22):​c.71-43A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,450,282 control chromosomes in the GnomAD database, including 14,240 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.12 (1383 hom., cov: 32)
  • Exomes 𝑓: 0.14 (12857 hom.)
• Consequence: MUC22 NM_001395414.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC22	NM_001395414.1	c.71-43A>G		intron_variant		ENST00000561890.1	NP_001382343.1
MUC22	NM_001198815.1	c.71-43A>G		intron_variant			NP_001185744.1
MUC22	NM_001318484.1	c.80-43A>G		intron_variant			NP_001305413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC22	ENST00000561890.1	c.71-43A>G		intron_variant		2	NM_001395414.1	ENSP00000455906	P1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18834 AN: 151934 Hom.: 1385 Cov.: 32

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.0935

Gnomad ASJ AF: 0.0916

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.110

GnomAD3 exomes AF: 0.154 AC: 9097 AN: 58988 Hom.: 900 AF XY: 0.155 AC XY: 4709 AN XY: 30358

Gnomad AFR exome AF: 0.0973

Gnomad AMR exome AF: 0.0887

Gnomad ASJ exome AF: 0.0902

Gnomad EAS exome AF: 0.319

Gnomad SAS exome AF: 0.202

Gnomad FIN exome AF: 0.140

Gnomad NFE exome AF: 0.133

Gnomad OTH exome AF: 0.139

GnomAD4 exome AF: 0.136 AC: 177144 AN: 1298228 Hom.: 12857 Cov.: 30 AF XY: 0.137 AC XY: 86519 AN XY: 632380

Gnomad4 AFR exome AF: 0.0934

Gnomad4 AMR exome AF: 0.0937

Gnomad4 ASJ exome AF: 0.0977

Gnomad4 EAS exome AF: 0.240

Gnomad4 SAS exome AF: 0.182

Gnomad4 FIN exome AF: 0.128

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.124 AC: 18826 AN: 152054 Hom.: 1383 Cov.: 32 AF XY: 0.126 AC XY: 9369 AN XY: 74330

Gnomad4 AFR AF: 0.0928

Gnomad4 AMR AF: 0.0931

Gnomad4 ASJ AF: 0.0916

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.111

Alfa AF: 0.112 Hom.: 483

Bravo AF: 0.118

Asia WGS AF: 0.208 AC: 722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.7
DANN	Benign	0.75
La Branchor		0.38

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: rs4713419; hg19: chr6-30993236;