dbSNP rs369670146: NCAPH:c.-1G>A (chr2-96335829-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_015341.5(NCAPH):c.-1G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000491 in 1,498,214 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00077 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00046 ( 12 hom. )

Consequence

NCAPH
NM_015341.5 5_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.563

Publications

1 publications found

Variant links:

Genes affected

NCAPH (HGNC:1112): (non-SMC condensin I complex subunit H) This gene encodes a member of the barr gene family and a regulatory subunit of the condensin complex. This complex is required for the conversion of interphase chromatin into condensed chromosomes. The protein encoded by this gene is associated with mitotic chromosomes, except during the early phase of chromosome condensation. During interphase, the protein has a distinct punctate nucleolar localization. Alternatively spliced transcript variants encoding different proteins have been described. [provided by RefSeq, Jul 2013]

NCAPH Gene-Disease associations (from GenCC):

microcephaly 23, primary, autosomal recessive
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

NCAPH links:

ENSG00000308585 (HGNC:):

ENSG00000308585 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 2-96335829-G-A is Benign according to our data. Variant chr2-96335829-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3035844.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015341.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NCAPH	NM_015341.5	MANE Select	c.-1G>A	5_prime_UTR	Exon 1 of 18	NP_056156.2
NCAPH	NM_001281710.2		c.-1G>A	5_prime_UTR	Exon 1 of 18	NP_001268639.1
NCAPH	NM_001281711.2		c.-1G>A	5_prime_UTR	Exon 1 of 18	NP_001268640.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NCAPH	ENST00000240423.9	TSL:1 MANE Select	c.-1G>A	5_prime_UTR	Exon 1 of 18	ENSP00000240423.4	Q15003-1
NCAPH	ENST00000435975.5	TSL:1	c.-1G>A	5_prime_UTR	Exon 1 of 14	ENSP00000405237.1	C9J470
NCAPH	ENST00000477409.1	TSL:1	n.29G>A	non_coding_transcript_exon	Exon 1 of 10

Frequencies

GnomAD3 genomes

AF:

0.000769

AC:

117

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0172

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000512

AC:

AN:

107326

AF XY:

0.000497

show subpopulations

Gnomad AFR exome

AF:

0.000613

Gnomad AMR exome

AF:

0.0000679

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0113

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000227

Gnomad OTH exome

AF:

0.000763

GnomAD4 exome

AF:

0.000460

AC:

619

AN:

1345900

Hom.:

Cov.:

AF XY:

0.000432

AC XY:

287

AN XY:

663974

show subpopulations

African (AFR)

AF:

0.000374

AC:

AN:

26712

American (AMR)

AF:

0.0000773

AC:

AN:

25862

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22996

East Asian (EAS)

AF:

0.0134

AC:

396

AN:

29500

South Asian (SAS)

AF:

0.000217

AC:

AN:

73684

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48278

Middle Eastern (MID)

AF:

0.000393

AC:

AN:

5092

European-Non Finnish (NFE)

AF:

0.00000756

AC:

AN:

1058522

Other (OTH)

AF:

0.00335

AC:

185

AN:

55254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

123

154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000768

AC:

117

AN:

152314

Hom.:

Cov.:

AF XY:

0.000873

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

41582

American (AMR)

AF:

0.000261

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0172

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68012

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000268

Hom.:

Bravo

AF:

0.000903

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

NCAPH-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.0

(source)

DANN

Benign

0.87

PhyloP100

-0.56

PromoterAI

0.037

Neutral

(source)

Mutation Taster

=300/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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