rs8181

Variant names:

• chr12-11171960-C-G
• rs8181
• NM_001271592.2:c.*397C>G

Variant summary

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

The NM_001271592.2(SMIM10L1):​c.*397C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 155,610 control chromosomes in the GnomAD database, including 45,979 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 0.75 (44756 hom., cov: 32)
  • Exomes 𝑓: 0.82 (1223 hom.)
• Consequence: SMIM10L1 NM_001271592.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379
• Publications: 11 publications found

Genes affected

SMIM10L1 (HGNC:49847): (small integral membrane protein 10 like 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMIM10L1	NM_001271592.2	c.*397C>G		3_prime_UTR_variant	Exon 1 of 1	ENST00000622602.2	NP_001258521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMIM10L1	ENST00000622602.2	c.*397C>G		3_prime_UTR_variant	Exon 1 of 1	6	NM_001271592.2	ENSP00000488907.1

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113353 AN: 151982 Hom.: 44743 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.962

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.925

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.770

GnomAD4 exome AF: 0.821 AC: 2882 AN: 3510 Hom.: 1223 Cov.: 0 AF XY: 0.828 AC XY: 1460 AN XY: 1764

African (AFR) AF: 0.407 AC: 79 AN: 194

American (AMR) AF: 0.775 AC: 62 AN: 80

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 128 AN: 150

East Asian (EAS) AF: 0.991 AC: 109 AN: 110

South Asian (SAS) AF: 0.794 AC: 27 AN: 34

European-Finnish (FIN) AF: 0.921 AC: 140 AN: 152

Middle Eastern (MID) AF: 0.833 AC: 10 AN: 12

European-Non Finnish (NFE) AF: 0.843 AC: 2154 AN: 2554

Other (OTH) AF: 0.772 AC: 173 AN: 224

GnomAD4 genome AF: 0.745 AC: 113382 AN: 152100 Hom.: 44756 Cov.: 32 AF XY: 0.755 AC XY: 56143 AN XY: 74356

African (AFR) AF: 0.455 AC: 18853 AN: 41408

American (AMR) AF: 0.826 AC: 12628 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 2917 AN: 3472

East Asian (EAS) AF: 0.961 AC: 4983 AN: 5184

South Asian (SAS) AF: 0.864 AC: 4161 AN: 4818

European-Finnish (FIN) AF: 0.925 AC: 9806 AN: 10598

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.844 AC: 57377 AN: 68010

Other (OTH) AF: 0.772 AC: 1632 AN: 2114

Alfa AF: 0.789 Hom.: 6112

Bravo AF: 0.725

Asia WGS AF: 0.899 AC: 3124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.4
DANN	Benign	0.62
PhyloP100		0.38
PromoterAI		-0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs8181; hg19: chr12-11324559;