chr22-45335658-C-T

Position:

• chr22-45335658-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.970+276C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 152,178 control chromosomes in the GnomAD database, including 55,640 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 0.85 (55640 hom., cov: 32)
• Consequence: FAM118A NM_017911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM118A	NM_017911.4	c.970+276C>T		intron_variant		ENST00000441876.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM118A	ENST00000441876.7	c.970+276C>T		intron_variant		1	NM_017911.4	P1

Frequencies

GnomAD3 genomes AF: 0.855 AC: 129975 AN: 152060 Hom.: 55601 Cov.: 32

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.823

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.851

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

GnomAD4 genome AF: 0.855 AC: 130070 AN: 152178 Hom.: 55640 Cov.: 32 AF XY: 0.847 AC XY: 63036 AN XY: 74380

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.881

Gnomad4 ASJ AF: 0.823

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.763

Gnomad4 FIN AF: 0.799

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.851

Alfa AF: 0.858 Hom.: 6948

Bravo AF: 0.862

Asia WGS AF: 0.778 AC: 2705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.49

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: rs738177; hg19: chr22-45731539;