rs3748748

Variant names:

• chr1-19691702-G-A
• rs3748748
• NM_181719.7:c.1500+2732C>T

Variant summary

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

The NM_181719.7(TMCO4):​c.1500+2732C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,134 control chromosomes in the GnomAD database, including 2,148 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 0.16 (2148 hom., cov: 32)
• Consequence: TMCO4 NM_181719.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• Publications: 8 publications found

Genes affected

TMCO4 (HGNC:27393): (transmembrane and coiled-coil domains 4) 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMCO4	NM_181719.7	c.1500+2732C>T		intron_variant	Intron 15 of 15	ENST00000294543.11	NP_859070.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMCO4	ENST00000294543.11	c.1500+2732C>T		intron_variant	Intron 15 of 15	1	NM_181719.7	ENSP00000294543.6
TMCO4	ENST00000375127.5	c.1500+2732C>T		intron_variant	Intron 14 of 15	1		ENSP00000364269.1
TMCO4	ENST00000489814.5	n.519+2732C>T		intron_variant	Intron 4 of 4	2

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24844 AN: 152016 Hom.: 2141 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.164 AC: 24876 AN: 152134 Hom.: 2148 Cov.: 32 AF XY: 0.164 AC XY: 12199 AN XY: 74374

African (AFR) AF: 0.203 AC: 8426 AN: 41482

American (AMR) AF: 0.128 AC: 1955 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 593 AN: 3470

East Asian (EAS) AF: 0.261 AC: 1352 AN: 5172

South Asian (SAS) AF: 0.167 AC: 805 AN: 4826

European-Finnish (FIN) AF: 0.117 AC: 1238 AN: 10604

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9874 AN: 67984

Other (OTH) AF: 0.153 AC: 322 AN: 2110

Alfa AF: 0.151 Hom.: 7360

Bravo AF: 0.165

Asia WGS AF: 0.199 AC: 690 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	3.4
DANN	Benign	0.56
PhyloP100		-0.014
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: rs3748748; hg19: chr1-20018195;