rs228787

Variant names:

• chr17-44022120-C-T
• rs228787
• ENST00000589334.5:c.-204+919G>A

Variant summary

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

The ENST00000589334.5(TMEM101):​c.-204+919G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 152,118 control chromosomes in the GnomAD database, including 41,982 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 0.72 (41982 hom., cov: 33)
• Consequence: TMEM101 ENST00000589334.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 6 publications found

Genes affected

TMEM101 (HGNC:28653): (transmembrane protein 101) Involved in positive regulation of I-kappaB kinase/NF-kappaB signaling. 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=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM101	NM_001304813.2	c.-210+919G>A		intron_variant	Intron 1 of 4		NP_001291742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM101	ENST00000589334.5	c.-204+919G>A		intron_variant	Intron 1 of 4	5		ENSP00000468025.1
TMEM101	ENST00000585950.5	c.-323-685G>A		intron_variant	Intron 1 of 4	3		ENSP00000466385.1
TMEM101	ENST00000592127.5	c.-210+919G>A		intron_variant	Intron 1 of 3	4		ENSP00000468388.1
TMEM101	ENST00000591162.1	n.376-685G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110220 AN: 152000 Hom.: 41961 Cov.: 33

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.725 AC: 110282 AN: 152118 Hom.: 41982 Cov.: 33 AF XY: 0.730 AC XY: 54309 AN XY: 74374

African (AFR) AF: 0.468 AC: 19404 AN: 41434

American (AMR) AF: 0.831 AC: 12701 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2715 AN: 3472

East Asian (EAS) AF: 0.934 AC: 4848 AN: 5190

South Asian (SAS) AF: 0.918 AC: 4440 AN: 4834

European-Finnish (FIN) AF: 0.780 AC: 8257 AN: 10588

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55310 AN: 68000

Other (OTH) AF: 0.756 AC: 1593 AN: 2106

Alfa AF: 0.751 Hom.: 8417

Bravo AF: 0.714

Asia WGS AF: 0.892 AC: 3100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Benign	0.93
PhyloP100		0.21
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: rs228787; hg19: chr17-42099488;