8-138367801-C-T

Position:

• chr8-138367801-C-T

Variant summary

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

The NM_015912.4(FAM135B):​c.77+106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0278 in 852,696 control chromosomes in the GnomAD database, including 959 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 0.032 (155 hom., cov: 32)
  • Exomes 𝑓: 0.027 (804 hom.)
• Consequence: FAM135B NM_015912.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

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]

FAM135B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM135B	NM_015912.4	c.77+106G>A		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+106G>A		intron_variant		5	NM_015912.4	ENSP00000378710.1

Frequencies

GnomAD3 genomes AF: 0.0321 AC: 4866 AN: 151748 Hom.: 154 Cov.: 32

Gnomad AFR AF: 0.0397

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0728

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0499

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.0274

GnomAD4 exome AF: 0.0269 AC: 18850 AN: 700830 Hom.: 804 AF XY: 0.0268 AC XY: 9861 AN XY: 368554

Gnomad4 AFR exome AF: 0.0402

Gnomad4 AMR exome AF: 0.0928

Gnomad4 ASJ exome AF: 0.00576

Gnomad4 EAS exome AF: 0.168

Gnomad4 SAS exome AF: 0.0407

Gnomad4 FIN exome AF: 0.0144

Gnomad4 NFE exome AF: 0.0121

Gnomad4 OTH exome AF: 0.0257

GnomAD4 genome AF: 0.0321 AC: 4881 AN: 151866 Hom.: 155 Cov.: 32 AF XY: 0.0339 AC XY: 2515 AN XY: 74224

Gnomad4 AFR AF: 0.0399

Gnomad4 AMR AF: 0.0728

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.0499

Gnomad4 FIN AF: 0.0129

Gnomad4 NFE AF: 0.0117

Gnomad4 OTH AF: 0.0266

Alfa AF: 0.0294 Hom.: 25

Bravo AF: 0.0380

Asia WGS AF: 0.0990 AC: 345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.7
DANN	Benign	0.73

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: rs10505702; hg19: chr8-139380044;