Genetic Variant NM_001387437.1:c.91C>T (chr1-103571693-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001387437.1(AMY2B):c.91C>T(p.Leu31Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00691 in 1,611,906 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0071 ( 56 hom. )

Consequence

AMY2B
NM_001387437.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.380

Publications

1 publications found

Variant links:

Genes affected

AMY2B (HGNC:478): (amylase alpha 2B) Amylases are secreted proteins that hydrolyze 1,4-alpha-glucoside bonds in oligosaccharides and polysaccharides, and thus catalyze the first step in digestion of dietary starch and glycogen. The human genome has a cluster of several amylase genes that are expressed at high levels in either salivary gland or pancreas. This gene encodes an amylase isoenzyme produced by the pancreas. [provided by RefSeq, Jun 2013]

AMY2B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 1-103571693-C-T is Benign according to our data. Variant chr1-103571693-C-T is described in ClinVar as Benign. ClinVar VariationId is 771690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.38 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387437.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMY2B	NM_001387437.1	MANE Select	c.91C>T	p.Leu31Leu	synonymous	Exon 1 of 10	NP_001374366.1	P19961-1
AMY2B	NM_001386109.1		c.91C>T	p.Leu31Leu	synonymous	Exon 3 of 12	NP_001373038.1	P19961-1
AMY2B	NM_020978.4		c.91C>T	p.Leu31Leu	synonymous	Exon 3 of 12	NP_066188.1	P19961-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AMY2B	ENST00000684275.1	MANE Select	c.91C>T	p.Leu31Leu	synonymous	Exon 1 of 10	ENSP00000507176.1	P19961-1
AMY2B	ENST00000361355.8	TSL:1	c.91C>T	p.Leu31Leu	synonymous	Exon 3 of 12	ENSP00000354610.4	P19961-1
AMY2B	ENST00000435302.5	TSL:3	c.91C>T	p.Leu31Leu	synonymous	Exon 3 of 4	ENSP00000391423.1	C9J2Z5

Frequencies

GnomAD3 genomes

AF:

0.00537

AC:

817

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00948

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00464

AC:

1161

AN:

250358

AF XY:

0.00484

show subpopulations

Gnomad AFR exome

AF:

0.00181

Gnomad AMR exome

AF:

0.00258

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00227

Gnomad NFE exome

AF:

0.00816

Gnomad OTH exome

AF:

0.00393

GnomAD4 exome

AF:

0.00707

AC:

10323

AN:

1459648

Hom.:

Cov.:

AF XY:

0.00692

AC XY:

5028

AN XY:

726124

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

33406

American (AMR)

AF:

0.00268

AC:

120

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00172

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39686

South Asian (SAS)

AF:

0.000940

AC:

AN:

86162

European-Finnish (FIN)

AF:

0.00234

AC:

125

AN:

53420

Middle Eastern (MID)

AF:

0.00145

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.00862

AC:

9583

AN:

1111792

Other (OTH)

AF:

0.00525

AC:

316

AN:

60202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

676

1353

2029

2706

3382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

352

704

1056

1408

1760

<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:

0.00537

AC:

817

AN:

152258

Hom.:

Cov.:

AF XY:

0.00484

AC XY:

360

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00118

AC:

AN:

41542

American (AMR)

AF:

0.00464

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00124

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00264

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00948

AC:

645

AN:

68024

Other (OTH)

AF:

0.00284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

108

144

180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00379

Hom.:

Bravo

AF:

0.00502

EpiCase

AF:

0.00758

EpiControl

AF:

0.00735

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

8.6

(source)

DANN

Benign

0.79

PhyloP100

0.38

PromoterAI

-0.028

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over