dbSNP rs600550: MS4A4E:c.-16-122G>A (chr11-60230193-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001393391.1(MS4A4E):c.-16-122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,085,806 control chromosomes in the GnomAD database, including 91,068 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 0.42 ( 13662 hom., cov: 31)

Exomes 𝑓: 0.40 ( 77406 hom. )

Consequence

MS4A4E
NM_001393391.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.04

Publications

23 publications found

Variant links:

COSMIC-nc: COSV67519073

Genes affected

MS4A4E (HGNC:14284): (membrane spanning 4-domains A4E) Most MS4A genes, including MS4A4E, encode proteins with at least 4 potential transmembrane domains and N- and C-terminal cytoplasmic domains encoded by distinct exons.[supplied by OMIM, Apr 2004]

MS4A4E links:

MS4A4A (HGNC:13371): (membrane spanning 4-domains A4A) This gene encodes a member of the membrane-spanning 4A gene family. Members of this nascent protein family are characterized by common structural features, similar intron/exon splice boundaries, and display unique expression patterns in hematopoietic cells and nonlymphoid tissues. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

MS4A4A 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=-1.01).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393391.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MS4A4E	NM_001393391.1	MANE Select	c.-16-122G>A		intron	N/A	NP_001380320.1	A0A494C1L8
	MS4A4E	NM_001351235.2		c.-89-122G>A		intron	N/A	NP_001338164.1	B4DT89

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MS4A4E	ENST00000651255.1	MANE Select	c.-16-122G>A	intron	N/A	ENSP00000499123.1	A0A494C1L8
MS4A4A	ENST00000649552.2		c.59+44022C>T	intron	N/A	ENSP00000497952.2	A0A3B3ITV6
MS4A4A	ENST00000679553.1		c.59+44022C>T	intron	N/A	ENSP00000505712.1	A0A7P0T9I4

Frequencies

GnomAD3 genomes

AF:

0.418

AC:

63440

AN:

151758

Hom.:

13648

Cov.:

show subpopulations

Gnomad AFR

AF:

0.411

Gnomad AMI

AF:

0.434

Gnomad AMR

AF:

0.415

Gnomad ASJ

AF:

0.327

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.612

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.411

Gnomad OTH

AF:

0.375

GnomAD4 exome

AF:

0.401

AC:

374291

AN:

933930

Hom.:

77406

AF XY:

0.396

AC XY:

182916

AN XY:

461486

show subpopulations

African (AFR)

AF:

0.408

AC:

8257

AN:

20246

American (AMR)

AF:

0.403

AC:

5740

AN:

14250

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

5159

AN:

16208

East Asian (EAS)

AF:

0.405

AC:

12281

AN:

30328

South Asian (SAS)

AF:

0.247

AC:

11308

AN:

45750

European-Finnish (FIN)

AF:

0.581

AC:

18897

AN:

32524

Middle Eastern (MID)

AF:

0.309

AC:

912

AN:

2956

European-Non Finnish (NFE)

AF:

0.405

AC:

295760

AN:

730104

Other (OTH)

AF:

0.384

AC:

15977

AN:

41564

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

10389

20779

31168

41558

51947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8536

17072

25608

34144

42680

<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:

0.418

AC:

63485

AN:

151876

Hom.:

13662

Cov.:

AF XY:

0.422

AC XY:

31356

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.410

AC:

16990

AN:

41398

American (AMR)

AF:

0.416

AC:

6341

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.327

AC:

1134

AN:

3472

East Asian (EAS)

AF:

0.414

AC:

2135

AN:

5156

South Asian (SAS)

AF:

0.253

AC:

1219

AN:

4818

European-Finnish (FIN)

AF:

0.612

AC:

6442

AN:

10522

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.411

AC:

27958

AN:

67942

Other (OTH)

AF:

0.375

AC:

793

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1829

3658

5488

7317

9146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

578

1156

1734

2312

2890

<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:

0.405

Hom.:

47638

Bravo

AF:

0.403

Asia WGS

AF:

0.332

AC:

1153

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.094

(source)

DANN

Benign

0.16

PhyloP100

-2.0

PromoterAI

-0.017

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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