rs10875423

Positions:

• chr8-138289135-T-A
• chr8-138289135-T-G

Variant summary

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

The NM_015912.4(FAM135B):​c.157+21706A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 152,118 control chromosomes in the GnomAD database, including 37,677 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 0.68 (37677 hom., cov: 33)
• Consequence: FAM135B NM_015912.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.589

Genes affected

FAM135B (HGNC:28029): (family with sequence similarity 135 member B) 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM135B	NM_015912.4	c.157+21706A>T		intron_variant		ENST00000395297.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM135B	ENST00000395297.6	c.157+21706A>T		intron_variant		5	NM_015912.4	P1

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103793 AN: 152000 Hom.: 37679 Cov.: 33

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.683 AC: 103828 AN: 152118 Hom.: 37677 Cov.: 33 AF XY: 0.677 AC XY: 50363 AN XY: 74356

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.780

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.810

Gnomad4 FIN AF: 0.763

Gnomad4 NFE AF: 0.826

Gnomad4 OTH AF: 0.713

Alfa AF: 0.750 Hom.: 5497

Bravo AF: 0.654

Asia WGS AF: 0.556 AC: 1936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.50

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: rs10875423; hg19: chr8-139301378;