8-138492027-C-T

Variant names:

• chr8-138492027-C-T
• rs11166827
• NM_015912.4:c.-20+4644G>A

Variant summary

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

The NM_015912.4(FAM135B):​c.-20+4644G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,062 control chromosomes in the GnomAD database, including 30,983 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 0.58 (30983 hom., cov: 32)
• Consequence: FAM135B NM_015912.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM135B	NM_015912.4	c.-20+4644G>A		intron_variant	Intron 1 of 19	ENST00000395297.6	NP_056996.2
FAM135B	NM_001362965.2	c.-20+5600G>A		intron_variant	Intron 1 of 19		NP_001349894.1
FAM135B	XM_011517061.3	c.-165+4644G>A		intron_variant	Intron 1 of 20		XP_011515363.1
FAM135B	XM_011517062.2	c.-20+4644G>A		intron_variant	Intron 1 of 19		XP_011515364.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM135B	ENST00000395297.6	c.-20+4644G>A		intron_variant	Intron 1 of 19	5	NM_015912.4	ENSP00000378710.1
FAM135B	ENST00000276737.10	n.-20+4644G>A		intron_variant	Intron 1 of 19	5		ENSP00000276737.6

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88582 AN: 151944 Hom.: 30980 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.583 AC: 88597 AN: 152062 Hom.: 30983 Cov.: 32 AF XY: 0.588 AC XY: 43707 AN XY: 74340

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.720

Gnomad4 ASJ AF: 0.805

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.759

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.644

Alfa AF: 0.708 Hom.: 31732

Bravo AF: 0.561

Asia WGS AF: 0.639 AC: 2220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11166827; hg19: chr8-139504270;