rs4461946

Positions:

• chr8-138180305-G-A

Variant summary

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

The NM_015912.4(FAM135B):​c.874-1615C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,968 control chromosomes in the GnomAD database, including 12,397 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 0.39 (12397 hom., cov: 32)
• Consequence: FAM135B NM_015912.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM135B	NM_015912.4	c.874-1615C>T		intron_variant		ENST00000395297.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM135B	ENST00000395297.6	c.874-1615C>T		intron_variant		5	NM_015912.4	P1
FAM135B	ENST00000482951.6	c.*820-1615C>T		intron_variant, NMD_transcript_variant		1
FAM135B	ENST00000276737.10	c.874-1615C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59498 AN: 151850 Hom.: 12358 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.392 AC: 59589 AN: 151968 Hom.: 12397 Cov.: 32 AF XY: 0.386 AC XY: 28641 AN XY: 74258

Gnomad4 AFR AF: 0.535

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.380

Alfa AF: 0.359 Hom.: 1247

Bravo AF: 0.400

Asia WGS AF: 0.320 AC: 1119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.22
DANN	Benign	0.66

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: rs4461946; hg19: chr8-139192548;