rs1668873

chr1-205266862-G-A

Variant summary

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

The NM_014858.4(TMCC2):c.748-2088G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,160 control chromosomes in the GnomAD database, including 6,484 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 0.27 (6484 hom., cov: 33)
• Consequence: TMCC2 NM_014858.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMCC2	NM_014858.4	c.748-2088G>A		intron_variant		ENST00000358024.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMCC2	ENST00000358024.8	c.748-2088G>A		intron_variant		1	NM_014858.4	P3

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40674 AN: 152040 Hom.: 6482 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.0409

Gnomad SAS AF: 0.0983

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.267 AC: 40689 AN: 152160 Hom.: 6484 Cov.: 33 AF XY: 0.263 AC XY: 19595 AN XY: 74382

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.0412

Gnomad4 SAS AF: 0.0982

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.267

Alfa AF: 0.334 Hom.: 10983

Bravo AF: 0.247

Asia WGS AF: 0.0620 AC: 220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.0
Dann	Benign	0.95

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: rs1668873; hg19: chr1-205235990;