chr6-24145668-C-T

Variant names:

• chr6-24145668-C-T
• rs11544636
• NM_080723.5:c.310C>T

Variant summary

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

The NM_080723.5(NRSN1):​c.310C>T​(p.His104Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0221 in 1,614,114 control chromosomes in the GnomAD database, including 493 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.017 (39 hom., cov: 32)
  • Exomes 𝑓: 0.023 (454 hom.)
• Consequence: NRSN1 NM_080723.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.13
• Publications: 10 publications found

Genes affected

NRSN1 (HGNC:17881): (neurensin 1) Predicted to be involved in nervous system development. Predicted to be located in cytoplasmic vesicle and growth cone. Predicted to be active in neuron projection; neuronal cell body; and transport vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037810206).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0165 (2515/152292) while in subpopulation SAS AF = 0.0338 (163/4820). AF 95% confidence interval is 0.0296. There are 39 homozygotes in GnomAd4. There are 1201 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 39 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080723.5. 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
	NRSN1	NM_080723.5	MANE Select	c.310C>T	p.His104Tyr	missense	Exon 4 of 4	NP_542454.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRSN1	ENST00000378491.9	TSL:1 MANE Select	c.310C>T	p.His104Tyr	missense	Exon 4 of 4	ENSP00000367752.4
	NRSN1	ENST00000378478.5	TSL:1	c.310C>T	p.His104Tyr	missense	Exon 4 of 4	ENSP00000367739.2
	NRSN1	ENST00000378477.2	TSL:1	c.310C>T	p.His104Tyr	missense	Exon 4 of 4	ENSP00000367738.2

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2515 AN: 152174 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.00357

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0340

Gnomad FIN AF: 0.0113

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0236

Gnomad OTH AF: 0.0149

GnomAD2 exomes AF: 0.0189 AC: 4750 AN: 251416 AF XY: 0.0203

Gnomad AFR exome AF: 0.00351

Gnomad AMR exome AF: 0.0133

Gnomad ASJ exome AF: 0.0259

Gnomad EAS exome AF: 0.000870

Gnomad FIN exome AF: 0.00919

Gnomad NFE exome AF: 0.0233

Gnomad OTH exome AF: 0.0215

GnomAD4 exome AF: 0.0226 AC: 33087 AN: 1461822 Hom.: 454 Cov.: 32 AF XY: 0.0233 AC XY: 16960 AN XY: 727212

African (AFR) AF: 0.00344 AC: 115 AN: 33478

American (AMR) AF: 0.0137 AC: 612 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0286 AC: 748 AN: 26134

East Asian (EAS) AF: 0.000680 AC: 27 AN: 39700

South Asian (SAS) AF: 0.0331 AC: 2859 AN: 86250

European-Finnish (FIN) AF: 0.0107 AC: 571 AN: 53420

Middle Eastern (MID) AF: 0.0238 AC: 137 AN: 5766

European-Non Finnish (NFE) AF: 0.0241 AC: 26817 AN: 1111960

Other (OTH) AF: 0.0199 AC: 1201 AN: 60392

GnomAD4 genome AF: 0.0165 AC: 2515 AN: 152292 Hom.: 39 Cov.: 32 AF XY: 0.0161 AC XY: 1201 AN XY: 74472

African (AFR) AF: 0.00356 AC: 148 AN: 41570

American (AMR) AF: 0.0156 AC: 238 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 93 AN: 3472

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5184

South Asian (SAS) AF: 0.0338 AC: 163 AN: 4820

European-Finnish (FIN) AF: 0.0113 AC: 120 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0237 AC: 1609 AN: 68020

Other (OTH) AF: 0.0147 AC: 31 AN: 2108

Alfa AF: 0.0211 Hom.: 110

Bravo AF: 0.0159

TwinsUK AF: 0.0227 AC: 84

ALSPAC AF: 0.0280 AC: 108

ESP6500AA AF: 0.00499 AC: 22

ESP6500EA AF: 0.0243 AC: 209

ExAC AF: 0.0191 AC: 2314

Asia WGS AF: 0.0130 AC: 45 AN: 3478

EpiCase AF: 0.0242

EpiControl AF: 0.0264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.090
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		6.1
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.097
Sift	Benign	0.039	D
Sift4G	Benign	0.074	T
Polyphen		0.26	B
Vest4		0.074
MPC		0.34
ClinPred		0.029	T
GERP RS		5.4
Varity_R		0.14
gMVP		0.61
Mutation Taster		=96/4	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: rs11544636; hg19: chr6-24145896; COSMIC: COSV99059235; COSMIC: COSV99059235;