4-123402583-T-C

Variant names:

• chr4-123402583-T-C
• rs300574
• NM_001258038.2:c.*32T>C

Variant summary

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

The NM_001258038.2(SPRY1):​c.*32T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 1,544,964 control chromosomes in the GnomAD database, including 320,597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (24469 hom., cov: 32)
  • Exomes 𝑓: 0.64 (296128 hom.)
• Consequence: SPRY1 NM_001258038.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.511
• Publications: 19 publications found

Genes affected

SPRY1 (HGNC:11269): (sprouty RTK signaling antagonist 1) Involved in negative regulation of fibroblast growth factor receptor signaling pathway. Located in Golgi apparatus; cytosol; and nucleoplasm. [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=-0.87).
• BP6: Variant 4-123402583-T-C is Benign according to our data. Variant chr4-123402583-T-C is described in ClinVar as Benign. ClinVar VariationId is 1270466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRY1	NM_001258038.2	c.*32T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000651917.1	NP_001244967.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPRY1	ENST00000651917.1	c.*32T>C		3_prime_UTR_variant	Exon 3 of 3		NM_001258038.2	ENSP00000498292.1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81798 AN: 151938 Hom.: 24464 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.554

GnomAD2 exomes AF: 0.582 AC: 120404 AN: 206964 AF XY: 0.588

Gnomad AFR exome AF: 0.271

Gnomad AMR exome AF: 0.477

Gnomad ASJ exome AF: 0.663

Gnomad EAS exome AF: 0.450

Gnomad FIN exome AF: 0.690

Gnomad NFE exome AF: 0.672

Gnomad OTH exome AF: 0.629

GnomAD4 exome AF: 0.645 AC: 897896 AN: 1392908 Hom.: 296128 Cov.: 41 AF XY: 0.641 AC XY: 439175 AN XY: 685550

African (AFR) AF: 0.263 AC: 8017 AN: 30512

American (AMR) AF: 0.479 AC: 14977 AN: 31264

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 14981 AN: 22650

East Asian (EAS) AF: 0.403 AC: 15660 AN: 38824

South Asian (SAS) AF: 0.461 AC: 35510 AN: 76962

European-Finnish (FIN) AF: 0.691 AC: 35659 AN: 51612

Middle Eastern (MID) AF: 0.560 AC: 3018 AN: 5392

European-Non Finnish (NFE) AF: 0.681 AC: 734963 AN: 1078566

Other (OTH) AF: 0.615 AC: 35111 AN: 57126

GnomAD4 genome AF: 0.538 AC: 81815 AN: 152056 Hom.: 24469 Cov.: 32 AF XY: 0.536 AC XY: 39826 AN XY: 74326

African (AFR) AF: 0.282 AC: 11693 AN: 41470

American (AMR) AF: 0.540 AC: 8244 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2293 AN: 3468

East Asian (EAS) AF: 0.428 AC: 2220 AN: 5182

South Asian (SAS) AF: 0.433 AC: 2086 AN: 4816

European-Finnish (FIN) AF: 0.685 AC: 7241 AN: 10566

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.679 AC: 46174 AN: 67966

Other (OTH) AF: 0.557 AC: 1172 AN: 2104

Alfa AF: 0.617 Hom.: 57573

Bravo AF: 0.517

Asia WGS AF: 0.414 AC: 1438 AN: 3478

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

- -

Jul 30, 2019

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	-0.87
CADD	Benign	8.7
DANN	Benign	0.61
PhyloP100		-0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs300574; hg19: chr4-124323738; COSMIC: COSV59338036; COSMIC: COSV59338036;