10-69630637-A-G

Position:

• chr10-69630637-A-G

Variant summary

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

The NM_145306.3(FAM241B):​c.-104+324A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,298,406 control chromosomes in the GnomAD database, including 33,363 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 0.17 (2658 hom., cov: 33)
  • Exomes 𝑓: 0.23 (30705 hom.)
• Consequence: FAM241B NM_145306.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110

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]

FAM241B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006044477).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM241B	NM_145306.3	c.-104+324A>G		intron_variant		ENST00000373279.6	NP_660349.1
FAM241B	XM_005269606.3	c.1A>G	p.Met1?	start_lost	1/4		XP_005269663.1
FAM241B	XM_005269608.4	c.-36+324A>G		intron_variant			XP_005269665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM241B	ENST00000373279.6	c.-104+324A>G		intron_variant		1	NM_145306.3	ENSP00000362376.4
FAM241B	ENST00000421716.1	c.1A>G	p.Met1?	start_lost	1/4	2		ENSP00000398621.1
FAM241B	ENST00000491890.1	n.63+324A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25974 AN: 151992 Hom.: 2655 Cov.: 33

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0380

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.168

GnomAD3 exomes AF: 0.189 AC: 27357 AN: 144800 Hom.: 3014 AF XY: 0.197 AC XY: 15329 AN XY: 77936

Gnomad AFR exome AF: 0.0703

Gnomad AMR exome AF: 0.135

Gnomad ASJ exome AF: 0.159

Gnomad EAS exome AF: 0.0333

Gnomad SAS exome AF: 0.251

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.226

Gnomad OTH exome AF: 0.178

GnomAD4 exome AF: 0.227 AC: 259793 AN: 1146296 Hom.: 30705 Cov.: 32 AF XY: 0.228 AC XY: 128262 AN XY: 562082

Gnomad4 AFR exome AF: 0.0705

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.160

Gnomad4 EAS exome AF: 0.0329

Gnomad4 SAS exome AF: 0.255

Gnomad4 FIN exome AF: 0.227

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.171 AC: 25981 AN: 152110 Hom.: 2658 Cov.: 33 AF XY: 0.169 AC XY: 12605 AN XY: 74372

Gnomad4 AFR AF: 0.0776

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.0379

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.169

Alfa AF: 0.201 Hom.: 2102

Bravo AF: 0.159

TwinsUK AF: 0.230 AC: 852

ALSPAC AF: 0.226 AC: 871

ExAC AF: 0.189 AC: 3946

Asia WGS AF: 0.160 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.9
DANN	Benign	0.45
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0060	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D
ClinPred		0.0024	T
GERP RS		-4.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs977096; hg19: chr10-71390393; COSMIC: COSV64768445;