Genetic Variant NM_198514.4:c.179-41T>C (chr10-113858487-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_198514.4(NHLRC2):c.179-41T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,419,310 control chromosomes in the GnomAD database, including 57,063 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 0.25 ( 5185 hom., cov: 32)

Exomes 𝑓: 0.28 ( 51878 hom. )

Consequence

NHLRC2
NM_198514.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0140

Publications

10 publications found

Variant links:

Genes affected

NHLRC2 (HGNC:24731): (NHL repeat containing 2) Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

NHLRC2 Gene-Disease associations (from GenCC):

fibrosis, neurodegeneration, and cerebral angiomatosis
Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

NHLRC2 links:

LOC124902506 (HGNC:):

LOC124902506 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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198514.4. 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
	NHLRC2	NM_198514.4	MANE Select	c.179-41T>C		intron	N/A	NP_940916.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NHLRC2	ENST00000369301.3	TSL:2 MANE Select	c.179-41T>C	intron	N/A	ENSP00000358307.3	Q8NBF2-1
NHLRC2	ENST00000918088.1		c.179-41T>C	intron	N/A	ENSP00000588147.1
NHLRC2	ENST00000866165.1		c.178+3437T>C	intron	N/A	ENSP00000536224.1

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38063

AN:

151888

Hom.:

5180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.329

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.390

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.288

Gnomad OTH

AF:

0.224

GnomAD2 exomes

AF:

0.282

AC:

55952

AN:

198354

AF XY:

0.279

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.272

Gnomad ASJ exome

AF:

0.226

Gnomad EAS exome

AF:

0.333

Gnomad FIN exome

AF:

0.397

Gnomad NFE exome

AF:

0.295

Gnomad OTH exome

AF:

0.274

GnomAD4 exome

AF:

0.282

AC:

357378

AN:

1267302

Hom.:

51878

Cov.:

AF XY:

0.280

AC XY:

178053

AN XY:

635602

show subpopulations

African (AFR)

AF:

0.140

AC:

3899

AN:

27842

American (AMR)

AF:

0.263

AC:

8760

AN:

33346

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

5009

AN:

22342

East Asian (EAS)

AF:

0.285

AC:

10891

AN:

38258

South Asian (SAS)

AF:

0.204

AC:

15162

AN:

74166

European-Finnish (FIN)

AF:

0.387

AC:

19765

AN:

51082

Middle Eastern (MID)

AF:

0.191

AC:

996

AN:

5222

European-Non Finnish (NFE)

AF:

0.290

AC:

278688

AN:

961746

Other (OTH)

AF:

0.267

AC:

14208

AN:

53298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

12101

24201

36302

48402

60503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8848

17696

26544

35392

44240

<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:

0.250

AC:

38075

AN:

152008

Hom.:

5185

Cov.:

AF XY:

0.253

AC XY:

18789

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.151

AC:

6261

AN:

41524

American (AMR)

AF:

0.255

AC:

3893

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

831

AN:

3464

East Asian (EAS)

AF:

0.330

AC:

1706

AN:

5170

South Asian (SAS)

AF:

0.200

AC:

966

AN:

4820

European-Finnish (FIN)

AF:

0.390

AC:

4111

AN:

10530

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.288

AC:

19554

AN:

67908

Other (OTH)

AF:

0.222

AC:

468

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1431

2862

4294

5725

7156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

400

800

1200

1600

2000

<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:

0.256

Hom.:

1887

Bravo

AF:

0.239

Asia WGS

AF:

0.253

AC:

877

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.7

(source)

DANN

Benign

0.54

PhyloP100

0.014

Mutation Taster

=100/0

polymorphism (auto)

(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