22-45322160-A-G

Position:

• chr22-45322160-A-G

Variant summary

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

The NM_001349916.2(FAM118A):​c.-23A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,490,466 control chromosomes in the GnomAD database, including 89,548 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 0.44 (18241 hom., cov: 32)
  • Exomes 𝑓: 0.31 (71307 hom.)
• Consequence: FAM118A NM_001349916.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245

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]

FAM118A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM118A	NM_017911.4	c.-9-211A>G		intron_variant		ENST00000441876.7	NP_060381.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM118A	ENST00000441876.7	c.-9-211A>G		intron_variant		1	NM_017911.4	ENSP00000395892.2

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67257 AN: 151810 Hom.: 18202 Cov.: 32

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.419

GnomAD3 exomes AF: 0.371 AC: 55655 AN: 149838 Hom.: 11539 AF XY: 0.374 AC XY: 30000 AN XY: 80304

Gnomad AFR exome AF: 0.779

Gnomad AMR exome AF: 0.381

Gnomad ASJ exome AF: 0.345

Gnomad EAS exome AF: 0.492

Gnomad SAS exome AF: 0.459

Gnomad FIN exome AF: 0.288

Gnomad NFE exome AF: 0.287

Gnomad OTH exome AF: 0.367

GnomAD4 exome AF: 0.310 AC: 414887 AN: 1338542 Hom.: 71307 Cov.: 30 AF XY: 0.313 AC XY: 206239 AN XY: 659236

Gnomad4 AFR exome AF: 0.781

Gnomad4 AMR exome AF: 0.385

Gnomad4 ASJ exome AF: 0.336

Gnomad4 EAS exome AF: 0.462

Gnomad4 SAS exome AF: 0.450

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.354

GnomAD4 genome AF: 0.443 AC: 67356 AN: 151924 Hom.: 18241 Cov.: 32 AF XY: 0.444 AC XY: 32943 AN XY: 74270

Gnomad4 AFR AF: 0.759

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.424

Alfa AF: 0.282 Hom.: 1518

Bravo AF: 0.464

Asia WGS AF: 0.516 AC: 1796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.35

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: rs1473953; hg19: chr22-45718041; COSMIC: COSV53417475;