rs2292948

Positions:

• chr10-73232856-T-C

Variant summary

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

The NM_173348.2(FAM149B1):​c.1128-83T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0832 in 819,028 control chromosomes in the GnomAD database, including 4,619 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 0.069 (624 hom., cov: 32)
  • Exomes 𝑓: 0.086 (3995 hom.)
• Consequence: FAM149B1 NM_173348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

Genes affected

FAM149B1 (HGNC:29162): (family with sequence similarity 149 member B1) Involved in cilium assembly and protein localization to cilium. Predicted to be located in cilium. Implicated in Joubert syndrome. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC9 (HGNC:19123): (DnaJ heat shock protein family (Hsp40) member C9) Enables chaperone binding activity; heat shock protein binding activity; and histone binding activity. Involved in nucleosome assembly and positive regulation of ATPase activity. Located in several cellular components, including cytosol; extracellular space; and nucleoplasm. Part of chaperone complex. [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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM149B1	NM_173348.2	c.1128-83T>C		intron_variant		ENST00000242505.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM149B1	ENST00000242505.11	c.1128-83T>C		intron_variant		5	NM_173348.2	P1

Frequencies

GnomAD3 genomes AF: 0.0692 AC: 10531 AN: 152174 Hom.: 625 Cov.: 32

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0714

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.0416

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0589

Gnomad OTH AF: 0.0617

GnomAD4 exome AF: 0.0864 AC: 57593 AN: 666736 Hom.: 3995 AF XY: 0.0927 AC XY: 32469 AN XY: 350192

Gnomad4 AFR exome AF: 0.0459

Gnomad4 AMR exome AF: 0.0775

Gnomad4 ASJ exome AF: 0.0952

Gnomad4 EAS exome AF: 0.284

Gnomad4 SAS exome AF: 0.212

Gnomad4 FIN exome AF: 0.0451

Gnomad4 NFE exome AF: 0.0602

Gnomad4 OTH exome AF: 0.0812

GnomAD4 genome AF: 0.0692 AC: 10542 AN: 152292 Hom.: 624 Cov.: 32 AF XY: 0.0718 AC XY: 5347 AN XY: 74460

Gnomad4 AFR AF: 0.0433

Gnomad4 AMR AF: 0.0715

Gnomad4 ASJ AF: 0.0922

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.0416

Gnomad4 NFE AF: 0.0589

Gnomad4 OTH AF: 0.0649

Alfa AF: 0.0633 Hom.: 62

Bravo AF: 0.0680

Asia WGS AF: 0.241 AC: 838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.2
DANN	Benign	0.64

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: rs2292948; hg19: chr10-74992614; COSMIC: COSV54351699; COSMIC: COSV54351699;