dbSNP rs11612037: NXPH4:c.57+2964C>T (chr12-57219990-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_007224.4(NXPH4):c.57+2964C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.033 in 152,542 control chromosomes in the GnomAD database, including 133 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 0.033 ( 132 hom., cov: 33)

Exomes 𝑓: 0.043 ( 1 hom. )

Consequence

NXPH4
NM_007224.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.04

Publications

5 publications found

Variant links:

Genes affected

NXPH4 (HGNC:8078): (neurexophilin 4) Predicted to enable signaling receptor binding activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

NXPH4 links:

Genome browser will be placed here

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=-0.79).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.033 (5023/152196) while in subpopulation NFE AF = 0.0511 (3476/68000). AF 95% confidence interval is 0.0497. There are 132 homozygotes in GnomAd4. There are 2403 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 132 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXPH4	NM_007224.4 link	c.57+2964C>T		intron_variant	Intron 1 of 1	ENST00000349394.6	NP_009155.1	O95158
NXPH4	XM_017018747.2 link	c.57+2964C>T		intron_variant	Intron 1 of 2		XP_016874236.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NXPH4	ENST00000349394.6 link	c.57+2964C>T	intron_variant	Intron 1 of 1	1	NM_007224.4	ENSP00000333593.6	O95158
NXPH4	ENST00000555154.1 link	n.108+14C>T	intron_variant	Intron 1 of 1	3
NXPH4	ENST00000556415.1 link	n.58-1317C>T	intron_variant	Intron 1 of 2	2		ENSP00000452288.1	G3V5C5

Frequencies

GnomAD3 genomes

AF:

0.0330

AC:

5023

AN:

152078

Hom.:

132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00800

Gnomad AMI

AF:

0.160

Gnomad AMR

AF:

0.0257

Gnomad ASJ

AF:

0.0254

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0466

Gnomad FIN

AF:

0.0284

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0511

Gnomad OTH

AF:

0.0282

GnomAD4 exome

AF:

0.0434

AC:

AN:

346

Hom.:

Cov.:

AF XY:

0.0413

AC XY:

AN XY:

218

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0204

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0545

AC:

AN:

202

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.537

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0330

AC:

5023

AN:

152196

Hom.:

132

Cov.:

AF XY:

0.0323

AC XY:

2403

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.00795

AC:

330

AN:

41506

American (AMR)

AF:

0.0257

AC:

393

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0254

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.0463

AC:

223

AN:

4820

European-Finnish (FIN)

AF:

0.0284

AC:

301

AN:

10602

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0511

AC:

3476

AN:

68000

Other (OTH)

AF:

0.0279

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

244

488

731

975

1219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0448

Hom.:

413

Bravo

AF:

0.0314

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.5

(source)

DANN

Benign

0.71

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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