rs742014

Positions:

• chr22-45329643-C-T

Variant summary

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

The NM_017911.4(FAM118A):​c.523-960C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,216 control chromosomes in the GnomAD database, including 18,775 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 (18771 hom., cov: 33)
  • Exomes 𝑓: 0.19 (4 hom.)
• Consequence: FAM118A NM_017911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM118A	NM_017911.4	c.523-960C>T		intron_variant		ENST00000441876.7	NP_060381.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM118A	ENST00000441876.7	c.523-960C>T		intron_variant		1	NM_017911.4	ENSP00000395892.2

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66871 AN: 152002 Hom.: 18732 Cov.: 33

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.416

GnomAD4 exome AF: 0.188 AC: 18 AN: 96 Hom.: 4 Cov.: 0 AF XY: 0.143 AC XY: 10 AN XY: 70

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.171

GnomAD4 genome AF: 0.440 AC: 66974 AN: 152120 Hom.: 18771 Cov.: 33 AF XY: 0.439 AC XY: 32637 AN XY: 74380

Gnomad4 AFR AF: 0.791

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.422

Alfa AF: 0.353 Hom.: 1553

Bravo AF: 0.465

Asia WGS AF: 0.508 AC: 1765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.29
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs742014; hg19: chr22-45725524;