Genetic Variant FAM241B:c.-104+324A>G (chr10-69630637-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.110

Publications

3 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145306.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM241B	NM_145306.3	MANE Select	c.-104+324A>G		intron	N/A	NP_660349.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FAM241B	ENST00000373279.6	TSL:1 MANE Select	c.-104+324A>G		intron	N/A	ENSP00000362376.4
FAM241B	ENST00000421716.1	TSL:2	c.1A>G	p.Met1?	start_lost	Exon 1 of 4	ENSP00000398621.1
FAM241B	ENST00000491890.1	TSL:3	n.63+324A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

25974

AN:

151992

Hom.:

2655

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.189

AC:

27357

AN:

144800

AF XY:

0.197

show subpopulations

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 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.:

AF XY:

0.228

AC XY:

128262

AN XY:

562082

show subpopulations

African (AFR)

AF:

0.0705

AC:

1708

AN:

24234

American (AMR)

AF:

0.137

AC:

3752

AN:

27378

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

2497

AN:

15654

East Asian (EAS)

AF:

0.0329

AC:

400

AN:

12156

South Asian (SAS)

AF:

0.255

AC:

19266

AN:

75504

European-Finnish (FIN)

AF:

0.227

AC:

6182

AN:

27292

Middle Eastern (MID)

AF:

0.162

AC:

709

AN:

4378

European-Non Finnish (NFE)

AF:

0.236

AC:

216984

AN:

918276

Other (OTH)

AF:

0.200

AC:

8295

AN:

41424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

8946

17892

26839

35785

44731

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8568

17136

25704

34272

42840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.171

AC:

25981

AN:

152110

Hom.:

2658

Cov.:

AF XY:

0.169

AC XY:

12605

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0776

AC:

3225

AN:

41534

American (AMR)

AF:

0.159

AC:

2426

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

548

AN:

3468

East Asian (EAS)

AF:

0.0379

AC:

195

AN:

5144

South Asian (SAS)

AF:

0.243

AC:

1171

AN:

4820

European-Finnish (FIN)

AF:

0.219

AC:

2319

AN:

10580

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.230

AC:

15626

AN:

67944

Other (OTH)

AF:

0.169

AC:

356

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1070

2139

3209

4278

5348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

292

584

876

1168

1460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.197

Hom.:

3153

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.9

(source)

DANN

Benign

0.45

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0014

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0060

MetaSVM

Benign

-1.0

PhyloP100

0.11

PROVEAN

Benign

-0.44

REVEL

Benign

0.11

Sift

Pathogenic

0.0

ClinPred

0.0024

GERP RS

-4.2

PromoterAI

0.089

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over