chr4-56467946-C-G

Variant names:

• chr4-56467946-C-G
• rs12505749
• NM_006947.4:c.109+202C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006947.4(SRP72):​c.109+202C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0754 in 152,266 control chromosomes in the GnomAD database, including 507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.075 (507 hom., cov: 32)
• Consequence: SRP72 NM_006947.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.992
• Publications: 10 publications found

Genes affected

SRP72 (HGNC:11303): (signal recognition particle 72) This gene encodes the 72 kDa subunit of the signal recognition particle (SRP), a ribonucleoprotein complex that mediates the targeting of secretory proteins to the endoplasmic reticulum (ER). The SRP complex consists of a 7S RNA and 6 protein subunits: SRP9, SRP14, SRP19, SRP54, SRP68, and SRP72, that are bound to the 7S RNA as monomers or heterodimers. SRP has at least 3 distinct functions that can be associated with the protein subunits: signal recognition, translational arrest, and ER membrane targeting by interaction with the docking protein. Mutations in this gene are associated with familial bone marrow failure. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

SRP72 Gene-Disease associations (from GenCC):

• autosomal dominant aplasia and myelodysplasia

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• acute myeloid leukemia

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp

ENSG00000289393 (HGNC:58796):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-56467946-C-G is Benign according to our data. Variant chr4-56467946-C-G is described in ClinVar as Benign. ClinVar VariationId is 1181159.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006947.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRP72	NM_006947.4	MANE Select	c.109+202C>G		intron	N/A	NP_008878.3
	SRP72	NM_001267722.2		c.109+202C>G		intron	N/A	NP_001254651.1
	SRP72	NR_151856.2		n.128+202C>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRP72	ENST00000642900.1	MANE Select	c.109+202C>G		intron	N/A	ENSP00000495128.1
	SRP72	ENST00000510663.6	TSL:1	c.109+202C>G		intron	N/A	ENSP00000424576.1
	ENSG00000289393	ENST00000687687.2		n.233G>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0755 AC: 11490 AN: 152146 Hom.: 507 Cov.: 32

Gnomad AFR AF: 0.0565

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.0509

Gnomad SAS AF: 0.0665

Gnomad FIN AF: 0.0824

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0780

Gnomad OTH AF: 0.0899

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

GnomAD4 genome AF: 0.0754 AC: 11487 AN: 152266 Hom.: 507 Cov.: 32 AF XY: 0.0764 AC XY: 5691 AN XY: 74458

African (AFR) AF: 0.0564 AC: 2344 AN: 41574

American (AMR) AF: 0.123 AC: 1878 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0709 AC: 246 AN: 3468

East Asian (EAS) AF: 0.0506 AC: 261 AN: 5154

South Asian (SAS) AF: 0.0655 AC: 316 AN: 4824

European-Finnish (FIN) AF: 0.0824 AC: 874 AN: 10608

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0780 AC: 5306 AN: 68018

Other (OTH) AF: 0.0884 AC: 187 AN: 2116

Alfa AF: 0.0300 Hom.: 18

Bravo AF: 0.0803

Asia WGS AF: 0.0620 AC: 217 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.74
PhyloP100		-0.99
PromoterAI		-0.0010	Neutral
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: rs12505749; hg19: chr4-57334112;