rs2064068

Variant names:

• chr22-45340604-C-T
• rs2064068
• NM_017911.4:c.*199C>T

Variant summary

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

The NM_017911.4(FAM118A):​c.*199C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 613,240 control chromosomes in the GnomAD database, including 73,072 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 0.40 (14619 hom., cov: 31)
  • Exomes 𝑓: 0.49 (58453 hom.)
• Consequence: FAM118A NM_017911.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 23 publications found

Genes affected

FAM118A (HGNC:1313): (family with sequence similarity 118 member A) Enables identical protein binding activity. Predicted to be integral component of membrane. [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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM118A	NM_017911.4	c.*199C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000441876.7	NP_060381.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM118A	ENST00000441876.7	c.*199C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_017911.4	ENSP00000395892.2

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60250 AN: 151828 Hom.: 14619 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.414

GnomAD4 exome AF: 0.492 AC: 227026 AN: 461294 Hom.: 58453 Cov.: 5 AF XY: 0.490 AC XY: 119666 AN XY: 244182

African (AFR) AF: 0.112 AC: 1422 AN: 12652

American (AMR) AF: 0.474 AC: 8902 AN: 18792

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 6775 AN: 13694

East Asian (EAS) AF: 0.394 AC: 12210 AN: 31002

South Asian (SAS) AF: 0.361 AC: 15502 AN: 42908

European-Finnish (FIN) AF: 0.486 AC: 17017 AN: 34996

Middle Eastern (MID) AF: 0.424 AC: 1493 AN: 3520

European-Non Finnish (NFE) AF: 0.546 AC: 151600 AN: 277452

Other (OTH) AF: 0.461 AC: 12105 AN: 26278

GnomAD4 genome AF: 0.397 AC: 60256 AN: 151946 Hom.: 14619 Cov.: 31 AF XY: 0.391 AC XY: 29055 AN XY: 74280

African (AFR) AF: 0.113 AC: 4691 AN: 41470

American (AMR) AF: 0.443 AC: 6758 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1716 AN: 3468

East Asian (EAS) AF: 0.339 AC: 1749 AN: 5166

South Asian (SAS) AF: 0.332 AC: 1598 AN: 4814

European-Finnish (FIN) AF: 0.468 AC: 4936 AN: 10552

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.550 AC: 37366 AN: 67894

Other (OTH) AF: 0.408 AC: 861 AN: 2108

Alfa AF: 0.496 Hom.: 25138

Bravo AF: 0.385

Asia WGS AF: 0.266 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.2
DANN	Benign	0.66
PhyloP100		-1.4
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: rs2064068; hg19: chr22-45736485; COSMIC: COSV53416966; COSMIC: COSV53416966;