chr1-205266862-G-A

Variant names:

• chr1-205266862-G-A
• rs1668873
• NM_014858.4:c.748-2088G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 39 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014858.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMCC2	NM_014858.4	MANE Select	c.748-2088G>A		intron	N/A	NP_055673.2
	TMCC2	NM_001242925.2		c.514-2088G>A		intron	N/A	NP_001229854.1
	TMCC2	NM_001375651.1		c.514-2088G>A		intron	N/A	NP_001362580.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMCC2	ENST00000358024.8	TSL:1 MANE Select	c.748-2088G>A		intron	N/A	ENSP00000350718.3
	TMCC2	ENST00000330675.12	TSL:1	c.163-2088G>A		intron	N/A	ENSP00000331842.7
	TMCC2	ENST00000637895.1	TSL:1	c.73-2088G>A		intron	N/A	ENSP00000490308.1

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

African (AFR) AF: 0.137 AC: 5700 AN: 41518

American (AMR) AF: 0.221 AC: 3376 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1018 AN: 3472

East Asian (EAS) AF: 0.0412 AC: 214 AN: 5190

South Asian (SAS) AF: 0.0982 AC: 474 AN: 4826

European-Finnish (FIN) AF: 0.414 AC: 4370 AN: 10566

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24677 AN: 67978

Other (OTH) AF: 0.267 AC: 564 AN: 2112

Alfa AF: 0.323 Hom.: 26826

Bravo AF: 0.247

Asia WGS AF: 0.0620 AC: 220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.0
DANN	Benign	0.95
PhyloP100		0.052
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: rs1668873; hg19: chr1-205235990;