chr14-21043338-C-T

Variant names:

• chr14-21043338-C-T
• rs1243469
• NM_032572.4:c.346C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032572.4(RNASE7):​c.346C>T​(p.His116Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 1,614,008 control chromosomes in the GnomAD database, including 618,677 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.86 (56409 hom., cov: 32)
  • Exomes 𝑓: 0.88 (562268 hom.)
• Consequence: RNASE7 NM_032572.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168
• Publications: 34 publications found

Genes affected

RNASE7 (HGNC:19278): (ribonuclease A family member 7) The protein encoded by this gene belongs to the pancreatic ribonuclease family, a subset of the ribonuclease A superfamily. The protein has broad-spectrum antimicrobial activity against bacteria and fungi. [provided by RefSeq, Oct 2014]

NDRG2 (HGNC:14460): (NDRG family member 2) This gene is a member of the N-myc downregulated gene family which belongs to the alpha/beta hydrolase superfamily. The protein encoded by this gene is a cytoplasmic protein that may play a role in neurite outgrowth. This gene may be involved in glioblastoma carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=8.2297834E-7).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032572.4. 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
	RNASE7	NM_032572.4	MANE Select	c.346C>T	p.His116Tyr	missense	Exon 2 of 2	NP_115961.3	Q9H1E1
	NDRG2	NM_001282211.2		c.25-20017G>A		intron	N/A	NP_001269140.1	Q9UN36-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASE7	ENST00000298690.5	TSL:1 MANE Select	c.346C>T	p.His116Tyr	missense	Exon 2 of 2	ENSP00000298690.3	Q9H1E1
	NDRG2	ENST00000949235.1		c.-17G>A		5_prime_UTR	Exon 1 of 16	ENSP00000619294.1
	NDRG2	ENST00000949236.1		c.-84G>A		5_prime_UTR	Exon 1 of 17	ENSP00000619295.1

Frequencies

GnomAD3 genomes AF: 0.859 AC: 130657 AN: 152068 Hom.: 56362 Cov.: 32

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.867

GnomAD2 exomes AF: 0.873 AC: 219245 AN: 251142 AF XY: 0.866

Gnomad AFR exome AF: 0.785

Gnomad AMR exome AF: 0.929

Gnomad ASJ exome AF: 0.943

Gnomad EAS exome AF: 0.863

Gnomad FIN exome AF: 0.937

Gnomad NFE exome AF: 0.888

Gnomad OTH exome AF: 0.879

GnomAD4 exome AF: 0.876 AC: 1280316 AN: 1461822 Hom.: 562268 Cov.: 59 AF XY: 0.872 AC XY: 634031 AN XY: 727206

African (AFR) AF: 0.783 AC: 26216 AN: 33480

American (AMR) AF: 0.925 AC: 41365 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 24580 AN: 26134

East Asian (EAS) AF: 0.891 AC: 35388 AN: 39700

South Asian (SAS) AF: 0.740 AC: 63848 AN: 86248

European-Finnish (FIN) AF: 0.937 AC: 50034 AN: 53414

Middle Eastern (MID) AF: 0.860 AC: 4963 AN: 5768

European-Non Finnish (NFE) AF: 0.883 AC: 981317 AN: 1111958

Other (OTH) AF: 0.871 AC: 52605 AN: 60396

GnomAD4 genome AF: 0.859 AC: 130761 AN: 152186 Hom.: 56409 Cov.: 32 AF XY: 0.859 AC XY: 63943 AN XY: 74400

African (AFR) AF: 0.786 AC: 32592 AN: 41490

American (AMR) AF: 0.903 AC: 13806 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3255 AN: 3472

East Asian (EAS) AF: 0.874 AC: 4521 AN: 5174

South Asian (SAS) AF: 0.744 AC: 3587 AN: 4824

European-Finnish (FIN) AF: 0.938 AC: 9946 AN: 10604

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.885 AC: 60163 AN: 68008

Other (OTH) AF: 0.869 AC: 1836 AN: 2112

Alfa AF: 0.875 Hom.: 198639

Bravo AF: 0.856

TwinsUK AF: 0.885 AC: 3282

ALSPAC AF: 0.882 AC: 3399

ESP6500AA AF: 0.791 AC: 3486

ESP6500EA AF: 0.885 AC: 7608

ExAC AF: 0.866 AC: 105173

Asia WGS AF: 0.825 AC: 2867 AN: 3478

EpiCase AF: 0.881

EpiControl AF: 0.890

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.042
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.3
DANN	Benign	0.89
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.00077	N
MetaRNN	Benign	8.2e-7	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-3.2	N
PhyloP100		0.17
PrimateAI	Benign	0.40	T
PROVEAN	Benign	4.5	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.070
MPC		0.24
ClinPred		0.0032	T
GERP RS		2.7
Varity_R		0.034
gMVP		0.41
Mutation Taster		=100/0	polymorphism (auto)

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: rs1243469; hg19: chr14-21511497; COSMIC: COSV53876841;