11-126268860-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_003139.4(SRPRA):c.-56C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 1,404,832 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (63 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (47 hom.)
• Consequence: SRPRA NM_003139.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.287

Genes affected

SRPRA (HGNC:11307): (SRP receptor subunit alpha) The gene encodes a subunit of the endoplasmic reticulum signal recognition particle receptor that, in conjunction with the signal recognition particle, is involved in the targeting and translocation of signal sequence tagged secretory and membrane proteins across the endoplasmic reticulum. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 11-126268860-G-A is Benign according to our data. Variant chr11-126268860-G-A is described in ClinVar as [Benign]. Clinvar id is 1287878.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0139 (2123/152330) while in subpopulation AFR AF= 0.0468 (1945/41570). AF 95% confidence interval is 0.0451. There are 63 homozygotes in gnomad4. There are 1008 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 2119 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRPRA	NM_003139.4	c.-56C>T		5_prime_UTR_variant	1/14	ENST00000332118.11
SRPRA	NM_001177842.2	c.-56C>T		5_prime_UTR_variant	1/13
SRPRA	XM_017018179.3	c.-56C>T		5_prime_UTR_variant	1/14
SRPRA	XM_047427497.1	c.-56C>T		5_prime_UTR_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRPRA	ENST00000332118.11	c.-56C>T		5_prime_UTR_variant	1/14	1	NM_003139.4	P1
SRPRA	ENST00000532259.1	c.-56C>T		5_prime_UTR_variant	1/13	2
SRPRA	ENST00000528744.5	n.61C>T		non_coding_transcript_exon_variant	1/3	2
SRPRA	ENST00000530680.1	n.167C>T		non_coding_transcript_exon_variant	2/4	4

Frequencies

GnomAD3 genomes AF: 0.0139 AC: 2119 AN: 152212 Hom.: 63 Cov.: 33

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00908

GnomAD4 exome AF: 0.00156 AC: 1948 AN: 1252502 Hom.: 47 Cov.: 18 AF XY: 0.00135 AC XY: 854 AN XY: 632532

Gnomad4 AFR exome AF: 0.0518

Gnomad4 AMR exome AF: 0.00291

Gnomad4 ASJ exome AF: 0.000371

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000885

Gnomad4 OTH exome AF: 0.00340

GnomAD4 genome AF: 0.0139 AC: 2123 AN: 152330 Hom.: 63 Cov.: 33 AF XY: 0.0135 AC XY: 1008 AN XY: 74490

Gnomad4 AFR AF: 0.0468

Gnomad4 AMR AF: 0.00516

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00716 Hom.: 4

Bravo AF: 0.0160

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
Cadd	Benign	16
Dann	Uncertain	0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12276901; hg19: chr11-126138755;