rs4823460

Positions:

• chr22-45323753-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.300+326C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,090 control chromosomes in the GnomAD database, including 17,190 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 0.43 (17190 hom., cov: 33)
• Consequence: FAM118A NM_017911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM118A	NM_017911.4	c.300+326C>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.300+326C>T		intron_variant		1	NM_017911.4	ENSP00000395892	P1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64980 AN: 151972 Hom.: 17189 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.427 AC: 64984 AN: 152090 Hom.: 17190 Cov.: 33 AF XY: 0.421 AC XY: 31302 AN XY: 74352

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.437

Alfa AF: 0.511 Hom.: 2766

Bravo AF: 0.413

Asia WGS AF: 0.274 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4823460; hg19: chr22-45719634;