rs2262274

Positions:

• chr10-69631951-C-T

Variant summary

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

The NM_145306.3(FAM241B):​c.96+112C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 151,912 control chromosomes in the GnomAD database, including 34,088 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 0.67 (34088 hom., cov: 31)
  • Exomes 𝑓: 0.68 (296954 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM241B NM_145306.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727

Genes affected

FAM241B (HGNC:23519): (family with sequence similarity 241 member B) Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM241B	NM_145306.3	c.96+112C>T		intron_variant		ENST00000373279.6
FAM241B	XM_005269606.3	c.222+112C>T		intron_variant
FAM241B	XM_005269608.4	c.96+112C>T		intron_variant
FAM241B	XM_011539455.3	c.96+112C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM241B	ENST00000373279.6	c.96+112C>T		intron_variant		1	NM_145306.3	P1
FAM241B	ENST00000421716.1	c.222+112C>T		intron_variant		2
FAM241B	ENST00000491890.1	n.423+112C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101190 AN: 151794 Hom.: 34051 Cov.: 31

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.662

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.681 AC: 864344 AN: 1269930 Hom.: 296954 AF XY: 0.680 AC XY: 425003 AN XY: 625360

Gnomad4 AFR exome AF: 0.624

Gnomad4 AMR exome AF: 0.815

Gnomad4 ASJ exome AF: 0.577

Gnomad4 EAS exome AF: 0.881

Gnomad4 SAS exome AF: 0.680

Gnomad4 FIN exome AF: 0.623

Gnomad4 NFE exome AF: 0.677

Gnomad4 OTH exome AF: 0.668

GnomAD4 genome AF: 0.667 AC: 101285 AN: 151912 Hom.: 34088 Cov.: 31 AF XY: 0.665 AC XY: 49392 AN XY: 74272

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.895

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.660

Alfa AF: 0.653 Hom.: 4042

Bravo AF: 0.679

Asia WGS AF: 0.784 AC: 2725 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	2.4
DANN	Benign	0.56

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: rs2262274; hg19: chr10-71391707; COSMIC: COSV64768719;