Genetic Variant NM_004617.4:c.-101A>G (chr3-149474777-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_004617.4(TM4SF4):c.-101A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 1,254,594 control chromosomes in the GnomAD database, including 373,206 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 0.64 ( 34918 hom., cov: 32)

Exomes 𝑓: 0.77 ( 338288 hom. )

Consequence

TM4SF4
NM_004617.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.672

Publications

4 publications found

Variant links:

Genes affected

TM4SF4 (HGNC:11856): (transmembrane 4 L six family member 4) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein that can regulate cell proliferation.[provided by RefSeq, Mar 2011]

TM4SF4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TM4SF4	NM_004617.4 link	c.-101A>G		5_prime_UTR_variant	Exon 1 of 5	ENST00000305354.5	NP_004608.1	P48230

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TM4SF4	ENST00000305354.5 link	c.-101A>G		5_prime_UTR_variant	Exon 1 of 5	1	NM_004617.4	ENSP00000305852.4		P48230
TM4SF4	ENST00000465758.1 link	c.-101A>G		5_prime_UTR_variant	Exon 1 of 2	3		ENSP00000419367.1		C9JVD2

Frequencies

GnomAD3 genomes

AF:

0.639

AC:

97090

AN:

151974

Hom.:

34922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.364

Gnomad AMI

AF:

0.815

Gnomad AMR

AF:

0.697

Gnomad ASJ

AF:

0.722

Gnomad EAS

AF:

0.0935

Gnomad SAS

AF:

0.439

Gnomad FIN

AF:

0.727

Gnomad MID

AF:

0.747

Gnomad NFE

AF:

0.827

Gnomad OTH

AF:

0.679

GnomAD4 exome

AF:

0.765

AC:

843919

AN:

1102500

Hom.:

338288

Cov.:

AF XY:

0.760

AC XY:

413601

AN XY:

544318

show subpopulations

African (AFR)

AF:

0.352

AC:

8813

AN:

25016

American (AMR)

AF:

0.663

AC:

13100

AN:

19762

Ashkenazi Jewish (ASJ)

AF:

0.716

AC:

12658

AN:

17680

East Asian (EAS)

AF:

0.122

AC:

4264

AN:

34958

South Asian (SAS)

AF:

0.465

AC:

25739

AN:

55328

European-Finnish (FIN)

AF:

0.737

AC:

35398

AN:

48004

Middle Eastern (MID)

AF:

0.756

AC:

2641

AN:

3492

European-Non Finnish (NFE)

AF:

0.831

AC:

707650

AN:

851102

Other (OTH)

AF:

0.714

AC:

33656

AN:

47158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

7903

15807

23710

31614

39517

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15364

30728

46092

61456

76820

<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:

0.638

AC:

97103

AN:

152094

Hom.:

34918

Cov.:

AF XY:

0.629

AC XY:

46800

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.364

AC:

15090

AN:

41468

American (AMR)

AF:

0.697

AC:

10656

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.722

AC:

2507

AN:

3472

East Asian (EAS)

AF:

0.0933

AC:

483

AN:

5176

South Asian (SAS)

AF:

0.438

AC:

2115

AN:

4828

European-Finnish (FIN)

AF:

0.727

AC:

7661

AN:

10544

Middle Eastern (MID)

AF:

0.755

AC:

222

AN:

294

European-Non Finnish (NFE)

AF:

0.827

AC:

56210

AN:

68000

Other (OTH)

AF:

0.672

AC:

1419

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1403

2806

4208

5611

7014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

740

1480

2220

2960

3700

<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:

0.766

Hom.:

57754

Bravo

AF:

0.628

Asia WGS

AF:

0.281

AC:

979

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.0

(source)

DANN

Benign

0.67

PhyloP100

0.67

PromoterAI

-0.062

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over