1-19707613-A-G

Position:

• chr1-19707613-A-G

Variant summary

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

The NM_181719.7(TMCO4):​c.1265-6728T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 152,200 control chromosomes in the GnomAD database, including 53,117 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 0.83 (53117 hom., cov: 31)
• Consequence: TMCO4 NM_181719.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMCO4	NM_181719.7	c.1265-6728T>C		intron_variant		ENST00000294543.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMCO4	ENST00000294543.11	c.1265-6728T>C		intron_variant		1	NM_181719.7	P1
TMCO4	ENST00000375127.5	c.1265-6728T>C		intron_variant		1
TMCO4	ENST00000489814.5	n.284-6728T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126332 AN: 152082 Hom.: 53050 Cov.: 31

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.812

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

GnomAD4 genome AF: 0.831 AC: 126461 AN: 152200 Hom.: 53117 Cov.: 31 AF XY: 0.829 AC XY: 61656 AN XY: 74412

Gnomad4 AFR AF: 0.955

Gnomad4 AMR AF: 0.838

Gnomad4 ASJ AF: 0.783

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.742

Gnomad4 NFE AF: 0.771

Gnomad4 OTH AF: 0.813

Alfa AF: 0.814 Hom.: 6571

Bravo AF: 0.842

Asia WGS AF: 0.840 AC: 2921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.68

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: rs3885191; hg19: chr1-20034106;