22-45322160-A-G

Variant names:

• chr22-45322160-A-G
• rs1473953
• NM_017911.4:c.-9-211A>G

Variant summary

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

The NM_017911.4(FAM118A):​c.-9-211A>G variant causes a intron 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_017911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245
• Publications: 17 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=-0.91).
• 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 rank	MANE	Protein	UniProt
FAM118A	NM_017911.4	c.-9-211A>G		intron_variant	Intron 1 of 8	ENST00000441876.7	NP_060381.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM118A	ENST00000441876.7	c.-9-211A>G		intron_variant	Intron 1 of 8	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

GnomAD2 exomes AF: 0.371 AC: 55655 AN: 149838 AF XY: 0.374

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 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

African (AFR) AF: 0.781 AC: 23544 AN: 30136

American (AMR) AF: 0.385 AC: 12853 AN: 33380

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 7838 AN: 23314

East Asian (EAS) AF: 0.462 AC: 14481 AN: 31314

South Asian (SAS) AF: 0.450 AC: 34799 AN: 77272

European-Finnish (FIN) AF: 0.290 AC: 12208 AN: 42082

Middle Eastern (MID) AF: 0.448 AC: 2418 AN: 5396

European-Non Finnish (NFE) AF: 0.276 AC: 287512 AN: 1041274

Other (OTH) AF: 0.354 AC: 19234 AN: 54374

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

African (AFR) AF: 0.759 AC: 31441 AN: 41410

American (AMR) AF: 0.429 AC: 6548 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1126 AN: 3468

East Asian (EAS) AF: 0.475 AC: 2447 AN: 5152

South Asian (SAS) AF: 0.470 AC: 2259 AN: 4806

European-Finnish (FIN) AF: 0.299 AC: 3160 AN: 10578

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19128 AN: 67936

Other (OTH) AF: 0.424 AC: 895 AN: 2110

Alfa AF: 0.440 Hom.: 8019

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
PhyloP100		-0.24
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: rs1473953; hg19: chr22-45718041; COSMIC: COSV53417475;