chr6-24144639-T-C

Variant names:

• chr6-24144639-T-C
• rs10946676
• NM_080723.5:c.190-909T>C

Variant summary

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

The NM_080723.5(NRSN1):​c.190-909T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 152,168 control chromosomes in the GnomAD database, including 62,057 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 0.90 (62057 hom., cov: 31)
• Consequence: NRSN1 NM_080723.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.45
• Publications: 2 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 (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRSN1	NM_080723.5	c.190-909T>C		intron_variant	Intron 3 of 3	ENST00000378491.9	NP_542454.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRSN1	ENST00000378491.9	c.190-909T>C		intron_variant	Intron 3 of 3	1	NM_080723.5	ENSP00000367752.4
NRSN1	ENST00000378478.5	c.190-909T>C		intron_variant	Intron 3 of 3	1		ENSP00000367739.2
NRSN1	ENST00000378477.2	c.190-909T>C		intron_variant	Intron 3 of 3	1		ENSP00000367738.2
NRSN1	ENST00000468195.2	n.256+10123T>C		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.898 AC: 136553 AN: 152050 Hom.: 62018 Cov.: 31

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.937

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.970

Gnomad FIN AF: 0.989

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.957

Gnomad OTH AF: 0.910

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.898 AC: 136650 AN: 152168 Hom.: 62057 Cov.: 31 AF XY: 0.901 AC XY: 67047 AN XY: 74384

African (AFR) AF: 0.741 AC: 30704 AN: 41460

American (AMR) AF: 0.937 AC: 14326 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 3084 AN: 3472

East Asian (EAS) AF: 0.995 AC: 5142 AN: 5166

South Asian (SAS) AF: 0.970 AC: 4671 AN: 4816

European-Finnish (FIN) AF: 0.989 AC: 10498 AN: 10616

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.957 AC: 65121 AN: 68038

Other (OTH) AF: 0.911 AC: 1922 AN: 2110

Alfa AF: 0.941 Hom.: 113528

Bravo AF: 0.886

Asia WGS AF: 0.961 AC: 3342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.20
PhyloP100		-3.5
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: rs10946676; hg19: chr6-24144867;