rs370701407

Variant names:

• chr19-38390455-C-T
• rs370701407
• NM_001394336.1:c.153C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-38390455-C-T
• chr19-38390455-C-A
• chr19-38390455-C-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_001394336.1(SPRED3):​c.153C>T​(p.His51His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000799 in 1,247,110 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00074 (2 hom., cov: 30)
  • Exomes 𝑓: 0.00081 (11 hom.)
• Consequence: SPRED3 NM_001394336.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.627
• Publications: 1 publications found

Genes affected

SPRED3 (HGNC:31041): (sprouty related EVH1 domain containing 3) This gene encodes a protein with a C-terminal Sprouty-like cysteine-rich domain (SRY) and an N-terminal Ena/Vasodilator-stimulated phosphoprotein (VASP) homology-1 (EVH-1) domain. The encoded protein is a member of a family of proteins that negatively regulates mitogen-activated protein (MAP) kinase signaling, particularly during organogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 19-38390455-C-T is Benign according to our data. Variant chr19-38390455-C-T is described in ClinVar as Benign. ClinVar VariationId is 735572.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.627 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000735 (109/148228) while in subpopulation SAS AF = 0.0238 (103/4326). AF 95% confidence interval is 0.0201. There are 2 homozygotes in GnomAd4. There are 73 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394336.1. 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
	SPRED3	NM_001394336.1	MANE Select	c.153C>T	p.His51His	synonymous	Exon 2 of 6	NP_001381265.1	Q2MJR0-1
	SPRED3	NM_001042522.3		c.153C>T	p.His51His	synonymous	Exon 1 of 5	NP_001035987.1	Q2MJR0-1
	SPRED3	NM_001394337.1		c.153C>T	p.His51His	synonymous	Exon 2 of 5	NP_001381266.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRED3	ENST00000691638.1	MANE Select	c.153C>T	p.His51His	synonymous	Exon 2 of 6	ENSP00000510478.1	Q2MJR0-1
	SPRED3	ENST00000338502.8	TSL:1	c.153C>T	p.His51His	synonymous	Exon 1 of 5	ENSP00000345405.4	Q2MJR0-1
	SPRED3	ENST00000587564.2	TSL:1	n.157C>T		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.000743 AC: 110 AN: 148104 Hom.: 2 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000134

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000447

Gnomad OTH AF: 0.000483

GnomAD2 exomes AF: 0.00217 AC: 167 AN: 76928 AF XY: 0.00282

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000286

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000816

Gnomad OTH exome AF: 0.000601

GnomAD4 exome AF: 0.000807 AC: 887 AN: 1098882 Hom.: 11 Cov.: 32 AF XY: 0.00112 AC XY: 596 AN XY: 534360

African (AFR) AF: 0.0000977 AC: 2 AN: 20464

American (AMR) AF: 0.000474 AC: 4 AN: 8434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14134

East Asian (EAS) AF: 0.00 AC: 0 AN: 18728

South Asian (SAS) AF: 0.0161 AC: 761 AN: 47398

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31764

Middle Eastern (MID) AF: 0.000762 AC: 3 AN: 3936

European-Non Finnish (NFE) AF: 0.0000766 AC: 70 AN: 913440

Other (OTH) AF: 0.00116 AC: 47 AN: 40584

GnomAD4 genome AF: 0.000735 AC: 109 AN: 148228 Hom.: 2 Cov.: 30 AF XY: 0.00101 AC XY: 73 AN XY: 72324

African (AFR) AF: 0.00 AC: 0 AN: 40574

American (AMR) AF: 0.000134 AC: 2 AN: 14896

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 4598

South Asian (SAS) AF: 0.0238 AC: 103 AN: 4326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000447 AC: 3 AN: 67156

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000355 Hom.: 0

Bravo AF: 0.000155

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.91
PhyloP100		0.63
PromoterAI		-0.018	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs370701407; hg19: chr19-38881095;