rs1172147

Variant names:

• chr1-205256329-G-A
• rs1172147
• NM_014858.4:c.748-12621G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-205256329-G-A
• chr1-205256329-G-C
• chr1-205256329-G-T

Variant summary

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

The NM_014858.4(TMCC2):​c.748-12621G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,550,110 control chromosomes in the GnomAD database, including 103,381 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 0.29 (7514 hom., cov: 33)
  • Exomes 𝑓: 0.36 (95867 hom.)
• Consequence: TMCC2 NM_014858.4 intron
• Scores: Splicing: ADA: 0.00006354
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 15 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.385 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMCC2	NM_014858.4	MANE Select	c.748-12621G>A		intron	N/A	NP_055673.2
	TMCC2	NM_001297613.2		c.-61G>A		5_prime_UTR	Exon 1 of 4	NP_001284542.1
	TMCC2	NM_001242925.2		c.514-12621G>A		intron	N/A	NP_001229854.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMCC2	ENST00000358024.8	TSL:1 MANE Select	c.748-12621G>A		intron	N/A	ENSP00000350718.3
	TMCC2	ENST00000637895.1	TSL:1	c.72+9638G>A		intron	N/A	ENSP00000490308.1
	TMCC2	ENST00000481950.2	TSL:1	n.72+9638G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43976 AN: 152092 Hom.: 7516 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.0534

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.305

GnomAD2 exomes AF: 0.283 AC: 42485 AN: 149896 AF XY: 0.279

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.217

Gnomad ASJ exome AF: 0.348

Gnomad EAS exome AF: 0.0499

Gnomad FIN exome AF: 0.409

Gnomad NFE exome AF: 0.389

Gnomad OTH exome AF: 0.328

GnomAD4 exome AF: 0.358 AC: 500006 AN: 1397900 Hom.: 95867 Cov.: 39 AF XY: 0.351 AC XY: 242282 AN XY: 689512

African (AFR) AF: 0.146 AC: 4623 AN: 31588

American (AMR) AF: 0.220 AC: 7863 AN: 35706

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 8684 AN: 25182

East Asian (EAS) AF: 0.0637 AC: 2278 AN: 35738

South Asian (SAS) AF: 0.121 AC: 9566 AN: 79212

European-Finnish (FIN) AF: 0.408 AC: 19679 AN: 48176

Middle Eastern (MID) AF: 0.228 AC: 1232 AN: 5410

European-Non Finnish (NFE) AF: 0.396 AC: 427738 AN: 1078878

Other (OTH) AF: 0.316 AC: 18343 AN: 58010

GnomAD4 genome AF: 0.289 AC: 43984 AN: 152210 Hom.: 7514 Cov.: 33 AF XY: 0.285 AC XY: 21173 AN XY: 74414

African (AFR) AF: 0.151 AC: 6259 AN: 41542

American (AMR) AF: 0.252 AC: 3855 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1170 AN: 3470

East Asian (EAS) AF: 0.0535 AC: 277 AN: 5178

South Asian (SAS) AF: 0.111 AC: 536 AN: 4826

European-Finnish (FIN) AF: 0.425 AC: 4497 AN: 10590

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26423 AN: 67992

Other (OTH) AF: 0.303 AC: 639 AN: 2112

Alfa AF: 0.355 Hom.: 42217

Bravo AF: 0.272

Asia WGS AF: 0.0860 AC: 305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.66
DANN	Benign	0.56
PhyloP100		-1.2
PromoterAI		-0.027	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000064
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.010		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: rs1172147; hg19: chr1-205225457; COSMIC: COSV58003392; COSMIC: COSV58003392;