8-138367721-T-C

Position:

• chr8-138367721-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.77+186A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.914 in 152,096 control chromosomes in the GnomAD database, including 64,239 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 0.91 (64239 hom., cov: 30)
• Consequence: FAM135B NM_015912.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM135B	NM_015912.4	c.77+186A>G		intron_variant		ENST00000395297.6	NP_056996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM135B	ENST00000395297.6	c.77+186A>G		intron_variant		5	NM_015912.4	ENSP00000378710	P1

Frequencies

GnomAD3 genomes AF: 0.914 AC: 138961 AN: 151978 Hom.: 64227 Cov.: 30

Gnomad AFR AF: 0.774

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.994

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.950

Gnomad FIN AF: 0.987

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.988

Gnomad OTH AF: 0.940

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

GnomAD4 genome AF: 0.914 AC: 139021 AN: 152096 Hom.: 64239 Cov.: 30 AF XY: 0.914 AC XY: 67967 AN XY: 74346

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.908

Gnomad4 ASJ AF: 0.994

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.950

Gnomad4 FIN AF: 0.987

Gnomad4 NFE AF: 0.987

Gnomad4 OTH AF: 0.938

Alfa AF: 0.965 Hom.: 51136

Bravo AF: 0.901

Asia WGS AF: 0.878 AC: 3054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.017
DANN	Benign	0.40

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: rs340707; hg19: chr8-139379964;