rs7901769

Variant names:

• chr10-113911577-G-A
• rs7901769
• NM_198514.4:c.*3041G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_198514.4(NHLRC2):​c.*3041G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 152,154 control chromosomes in the GnomAD database, including 30 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 0.011 (30 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: NHLRC2 NM_198514.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• Publications: 1 publications found

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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0111 (1689/152154) while in subpopulation AFR AF = 0.0368 (1528/41542). AF 95% confidence interval is 0.0352. There are 30 homozygotes in GnomAd4. There are 794 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 30 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHLRC2	NM_198514.4	MANE Select	c.*3041G>A		3_prime_UTR	Exon 11 of 11	NP_940916.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHLRC2	ENST00000369301.3	TSL:2 MANE Select	c.*3041G>A		3_prime_UTR	Exon 11 of 11	ENSP00000358307.3

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1682 AN: 152036 Hom.: 28 Cov.: 33

Gnomad AFR AF: 0.0366

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00726

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0105

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0111 AC: 1689 AN: 152154 Hom.: 30 Cov.: 33 AF XY: 0.0107 AC XY: 794 AN XY: 74362

African (AFR) AF: 0.0368 AC: 1528 AN: 41542

American (AMR) AF: 0.00523 AC: 80 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00727 AC: 35 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67958

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.0103 Hom.: 7

Bravo AF: 0.0122

Asia WGS AF: 0.00466 AC: 16 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.98
DANN	Benign	0.52
PhyloP100		0.062
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs7901769; hg19: chr10-115671336;