ENST00000648708.1:n.114-2203G>A

Variant names:

• chr1-205275825-G-A
• rs1172130
• ENST00000648708.1:n.114-2203G>A

Variant summary

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

The ENST00000648708.1(TMCC2):​n.114-2203G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,058 control chromosomes in the GnomAD database, including 7,607 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 0.30 (7607 hom., cov: 32)
• Consequence: TMCC2 ENST00000648708.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916

Genes affected

TMCC2 (HGNC:24239): (transmembrane and coiled-coil domain family 2) Involved in amyloid precursor protein metabolic process. Located in endoplasmic reticulum. [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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMCC2	ENST00000648708.1	n.114-2203G>A		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44974 AN: 151938 Hom.: 7606 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.296 AC: 44976 AN: 152058 Hom.: 7607 Cov.: 32 AF XY: 0.293 AC XY: 21781 AN XY: 74316

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.295

Alfa AF: 0.356 Hom.: 9625

Bravo AF: 0.275

Asia WGS AF: 0.125 AC: 439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.34
DANN	Benign	0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1172130; hg19: chr1-205244953;