rs104664

Positions:

• chr22-45315973-G-A
• chr22-45315973-G-C

Variant summary

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

The NM_017911.4(FAM118A):​c.-10+5790G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 152,210 control chromosomes in the GnomAD database, including 58,936 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 0.88 (58936 hom., cov: 33)
• Consequence: FAM118A NM_017911.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM118A	NM_017911.4	c.-10+5790G>A		intron_variant		ENST00000441876.7	NP_060381.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM118A	ENST00000441876.7	c.-10+5790G>A		intron_variant		1	NM_017911.4	ENSP00000395892	P1
FAM118A	ENST00000216214.7	c.-10+5790G>A		intron_variant		2		ENSP00000216214	P1
FAM118A	ENST00000405673.5	c.-10+5790G>A		intron_variant		5		ENSP00000385231
FAM118A	ENST00000477714.1	n.47+5790G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133648 AN: 152092 Hom.: 58876 Cov.: 33

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.867

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

GnomAD4 genome AF: 0.879 AC: 133767 AN: 152210 Hom.: 58936 Cov.: 33 AF XY: 0.871 AC XY: 64782 AN XY: 74392

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.873

Gnomad4 ASJ AF: 0.829

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.800

Gnomad4 NFE AF: 0.873

Gnomad4 OTH AF: 0.867

Alfa AF: 0.874 Hom.: 84044

Bravo AF: 0.888

Asia WGS AF: 0.783 AC: 2724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.18
DANN	Benign	0.27

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: rs104664; hg19: chr22-45711854;