rs4909764

chr8-138243675-T-C

Variant summary

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

The NM_015912.4(FAM135B):c.543-607A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0571 in 152,276 control chromosomes in the GnomAD database, including 297 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 0.057 (297 hom., cov: 33)
• Consequence: FAM135B NM_015912.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM135B	NM_015912.4	c.543-607A>G		intron_variant		ENST00000395297.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM135B	ENST00000395297.6	c.543-607A>G		intron_variant		5	NM_015912.4	P1
FAM135B	ENST00000482951.6	c.*489-607A>G		intron_variant, NMD_transcript_variant		1
FAM135B	ENST00000276737.10	c.543-607A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0570 AC: 8672 AN: 152158 Hom.: 290 Cov.: 33

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0694

Gnomad EAS AF: 0.0602

Gnomad SAS AF: 0.0454

Gnomad FIN AF: 0.0650

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0435

Gnomad OTH AF: 0.0650

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

GnomAD4 genome AF: 0.0571 AC: 8698 AN: 152276 Hom.: 297 Cov.: 33 AF XY: 0.0589 AC XY: 4385 AN XY: 74452

Gnomad4 AFR AF: 0.0611

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0694

Gnomad4 EAS AF: 0.0603

Gnomad4 SAS AF: 0.0448

Gnomad4 FIN AF: 0.0650

Gnomad4 NFE AF: 0.0435

Gnomad4 OTH AF: 0.0691

Alfa AF: 0.0486 Hom.: 263

Bravo AF: 0.0615

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.072
Dann	Benign	0.78

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: rs4909764; hg19: chr8-139255918;