NM_003162.4:c.1547+12T>C

Variant names:

• chr2-36867802-A-G
• rs2540923
• NM_003162.4:c.1547+12T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003162.4(STRN):​c.1547+12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.974 in 1,532,196 control chromosomes in the GnomAD database, including 728,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (64484 hom., cov: 32)
  • Exomes 𝑓: 0.98 (664321 hom.)
• Consequence: STRN NM_003162.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.16
• Publications: 17 publications found

Genes affected

STRN (HGNC:11424): (striatin) Enables armadillo repeat domain binding activity; estrogen receptor binding activity; and protein phosphatase 2A binding activity. Involved in Wnt signaling pathway and negative regulation of cell population proliferation. Located in bicellular tight junction. Part of FAR/SIN/STRIPAK complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-36867802-A-G is Benign according to our data. Variant chr2-36867802-A-G is described in ClinVar as Benign. ClinVar VariationId is 1239451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRN	NM_003162.4	c.1547+12T>C		intron_variant	Intron 12 of 17	ENST00000263918.9	NP_003153.2
STRN	XM_011533073.3	c.1634+12T>C		intron_variant	Intron 13 of 18		XP_011531375.1
STRN	XM_005264519.6	c.1436+12T>C		intron_variant	Intron 11 of 16		XP_005264576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRN	ENST00000263918.9	c.1547+12T>C		intron_variant	Intron 12 of 17	1	NM_003162.4	ENSP00000263918.4

Frequencies

GnomAD3 genomes AF: 0.914 AC: 138973 AN: 152070 Hom.: 64458 Cov.: 32

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.940

Gnomad AMR AF: 0.959

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.987

Gnomad FIN AF: 0.978

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.937

GnomAD2 exomes AF: 0.970 AC: 205343 AN: 211704 AF XY: 0.975

Gnomad AFR exome AF: 0.735

Gnomad AMR exome AF: 0.984

Gnomad ASJ exome AF: 0.998

Gnomad EAS exome AF: 0.999

Gnomad FIN exome AF: 0.979

Gnomad NFE exome AF: 0.986

Gnomad OTH exome AF: 0.981

GnomAD4 exome AF: 0.980 AC: 1352889 AN: 1380008 Hom.: 664321 Cov.: 22 AF XY: 0.981 AC XY: 674768 AN XY: 687616

African (AFR) AF: 0.729 AC: 21785 AN: 29892

American (AMR) AF: 0.980 AC: 33989 AN: 34680

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 24090 AN: 24158

East Asian (EAS) AF: 0.999 AC: 36924 AN: 36944

South Asian (SAS) AF: 0.989 AC: 74137 AN: 74944

European-Finnish (FIN) AF: 0.980 AC: 49824 AN: 50834

Middle Eastern (MID) AF: 0.976 AC: 5380 AN: 5514

European-Non Finnish (NFE) AF: 0.986 AC: 1051485 AN: 1066084

Other (OTH) AF: 0.970 AC: 55275 AN: 56958

GnomAD4 genome AF: 0.914 AC: 139046 AN: 152188 Hom.: 64484 Cov.: 32 AF XY: 0.916 AC XY: 68140 AN XY: 74406

African (AFR) AF: 0.733 AC: 30406 AN: 41470

American (AMR) AF: 0.959 AC: 14670 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 3460 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5179 AN: 5184

South Asian (SAS) AF: 0.987 AC: 4763 AN: 4824

European-Finnish (FIN) AF: 0.978 AC: 10376 AN: 10612

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.986 AC: 67074 AN: 68018

Other (OTH) AF: 0.937 AC: 1978 AN: 2110

Alfa AF: 0.968 Hom.: 91602

Bravo AF: 0.903

Asia WGS AF: 0.976 AC: 3380 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.51
DANN	Benign	0.80
PhyloP100		-1.2
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: rs2540923; hg19: chr2-37094945; COSMIC: COSV55745584; COSMIC: COSV55745584;