Genetic Variant NM_181606.3:c.66T>C (chr21-30829633-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_181606.3(KRTAP7-1):c.66T>C(p.His22His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,550,838 control chromosomes in the GnomAD database, including 188,527 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 0.49 ( 18327 hom., cov: 32)

Exomes 𝑓: 0.49 ( 170200 hom. )

Consequence

KRTAP7-1
NM_181606.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.82

Publications

14 publications found

Variant links:

Genes affected

KRTAP7-1 (HGNC:18934): (keratin associated protein 7-1) Predicted to be located in intermediate filament. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP7-1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP7

Synonymous conserved (PhyloP=-1.82 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP7-1	NM_181606.3 link	c.66T>C	p.His22His	synonymous_variant	Exon 1 of 1	ENST00000621162.1	NP_853637.2	Q8IUC3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP7-1	ENST00000621162.1 link	c.66T>C	p.His22His	synonymous_variant	Exon 1 of 1	6	NM_181606.3	ENSP00000479656.1		Q8IUC3

Frequencies

GnomAD3 genomes

AF:

0.487

AC:

73971

AN:

151872

Hom.:

18304

Cov.:

show subpopulations

Gnomad AFR

AF:

0.438

Gnomad AMI

AF:

0.462

Gnomad AMR

AF:

0.600

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.445

Gnomad SAS

AF:

0.534

Gnomad FIN

AF:

0.523

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.489

Gnomad OTH

AF:

0.502

GnomAD2 exomes

AF:

0.526

AC:

80354

AN:

152690

AF XY:

0.520

show subpopulations

Gnomad AFR exome

AF:

0.434

Gnomad AMR exome

AF:

0.709

Gnomad ASJ exome

AF:

0.429

Gnomad EAS exome

AF:

0.461

Gnomad FIN exome

AF:

0.514

Gnomad NFE exome

AF:

0.489

Gnomad OTH exome

AF:

0.509

GnomAD4 exome

AF:

0.491

AC:

686921

AN:

1398848

Hom.:

170200

Cov.:

AF XY:

0.492

AC XY:

339426

AN XY:

689942

show subpopulations

African (AFR)

AF:

0.433

AC:

13666

AN:

31588

American (AMR)

AF:

0.691

AC:

24641

AN:

35662

Ashkenazi Jewish (ASJ)

AF:

0.433

AC:

10894

AN:

25166

East Asian (EAS)

AF:

0.482

AC:

17198

AN:

35712

South Asian (SAS)

AF:

0.532

AC:

42142

AN:

79180

European-Finnish (FIN)

AF:

0.516

AC:

25431

AN:

49266

Middle Eastern (MID)

AF:

0.482

AC:

2744

AN:

5694

European-Non Finnish (NFE)

AF:

0.484

AC:

522417

AN:

1078600

Other (OTH)

AF:

0.479

AC:

27788

AN:

57980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

17234

34469

51703

68938

86172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15620

31240

46860

62480

78100

<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:

0.487

AC:

74042

AN:

151990

Hom.:

18327

Cov.:

AF XY:

0.489

AC XY:

36356

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.439

AC:

18180

AN:

41458

American (AMR)

AF:

0.600

AC:

9175

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.427

AC:

1480

AN:

3468

East Asian (EAS)

AF:

0.445

AC:

2291

AN:

5148

South Asian (SAS)

AF:

0.534

AC:

2568

AN:

4810

European-Finnish (FIN)

AF:

0.523

AC:

5514

AN:

10550

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.489

AC:

33215

AN:

67962

Other (OTH)

AF:

0.503

AC:

1060

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1944

3888

5832

7776

9720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

676

1352

2028

2704

3380

<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:

0.481

Hom.:

40199

Bravo

AF:

0.491

Asia WGS

AF:

0.497

AC:

1729

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.3

(source)

DANN

Benign

0.80

PhyloP100

-1.8

PromoterAI

0.011

Neutral

(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