1-205280322-A-G

Variant names:

• chr1-205280322-A-G
• rs9660992
• ENST00000648708.1:n.432-27A>G

Variant summary

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

The ENST00000648708.1(TMCC2):​n.432-27A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 151,910 control chromosomes in the GnomAD database, including 14,441 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 0.42 (14441 hom., cov: 31)
• Consequence: TMCC2 ENST00000648708.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• Publications: 28 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000648708.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMCC2	ENST00000648708.1		n.432-27A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64090 AN: 151792 Hom.: 14412 Cov.: 31

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.422 AC: 64162 AN: 151910 Hom.: 14441 Cov.: 31 AF XY: 0.415 AC XY: 30792 AN XY: 74234

African (AFR) AF: 0.535 AC: 22162 AN: 41412

American (AMR) AF: 0.296 AC: 4513 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1210 AN: 3472

East Asian (EAS) AF: 0.139 AC: 718 AN: 5152

South Asian (SAS) AF: 0.152 AC: 733 AN: 4822

European-Finnish (FIN) AF: 0.455 AC: 4788 AN: 10530

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28874 AN: 67940

Other (OTH) AF: 0.393 AC: 829 AN: 2110

Alfa AF: 0.416 Hom.: 38678

Bravo AF: 0.414

Asia WGS AF: 0.163 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	8.2
DANN	Benign	0.57
PhyloP100		0.22

Splicing

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

Other links and lift over

dbSNP: rs9660992; hg19: chr1-205249450;