rs11066119

Variant names:

• chr12-111996700-A-G
• rs11066119
• NM_001193531.2:c.79-4811T>C

Variant summary

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

The NM_001193531.2(TMEM116):​c.79-4811T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,168 control chromosomes in the GnomAD database, including 2,031 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 0.14 (2031 hom., cov: 32)
• Consequence: TMEM116 NM_001193531.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• Publications: 19 publications found

Genes affected

TMEM116 (HGNC:25084): (transmembrane protein 116) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM116	NM_001193531.2	c.79-4811T>C		intron_variant	Intron 3 of 10	ENST00000552374.7	NP_001180460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM116	ENST00000552374.7	c.79-4811T>C		intron_variant	Intron 3 of 10	1	NM_001193531.2	ENSP00000447731.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22030 AN: 152050 Hom.: 2028 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0886

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0928

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.145 AC: 22052 AN: 152168 Hom.: 2031 Cov.: 32 AF XY: 0.144 AC XY: 10707 AN XY: 74424

African (AFR) AF: 0.259 AC: 10762 AN: 41474

American (AMR) AF: 0.0884 AC: 1353 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3470

East Asian (EAS) AF: 0.239 AC: 1237 AN: 5186

South Asian (SAS) AF: 0.159 AC: 769 AN: 4828

European-Finnish (FIN) AF: 0.112 AC: 1187 AN: 10594

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0928 AC: 6311 AN: 67996

Other (OTH) AF: 0.126 AC: 267 AN: 2112

Alfa AF: 0.107 Hom.: 1200

Bravo AF: 0.149

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.96
PhyloP100		1.5
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: rs11066119; hg19: chr12-112434504;