rs9455158

Positions:

• chr6-70561176-C-A
• chr6-70561176-C-G

Variant summary

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

The 6-70561176-C-A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 151,872 control chromosomes in the GnomAD database, including 6,824 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 0.27 (6822 hom., cov: 33)
  • Exomes 𝑓: 0.18 (2 hom.)
• Consequence: FAM135A NM_001162529.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

Genes affected

FAM135A (HGNC:21084): (family with sequence similarity 135 member A) Predicted to be involved in cellular lipid metabolic process. [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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM135A	NM_001162529.3			downstream_gene_variant		ENST00000418814.7	NP_001156001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM135A	ENST00000418814.7			downstream_gene_variant		5	NM_001162529.3	ENSP00000410768	A1
FAM135A	ENST00000370479.7			downstream_gene_variant		1		ENSP00000359510	A1
FAM135A	ENST00000505675.1			downstream_gene_variant		1
FAM135A	ENST00000194672.11			downstream_gene_variant		5		ENSP00000194672

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40235 AN: 151638 Hom.: 6785 Cov.: 33

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.0650

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0945

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.253

GnomAD4 exome AF: 0.178 AC: 21 AN: 118 Hom.: 2 Cov.: 0 AF XY: 0.125 AC XY: 9 AN XY: 72

Gnomad4 FIN exome AF: 0.181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.266 AC: 40326 AN: 151754 Hom.: 6822 Cov.: 33 AF XY: 0.265 AC XY: 19615 AN XY: 74134

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0941

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.256

Alfa AF: 0.245 Hom.: 840

Bravo AF: 0.271

Asia WGS AF: 0.208 AC: 723 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.7
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9455158; hg19: chr6-71270879;