rs201389647

Variant names:

• chr11-61430199-T-C
• rs201389647
• NM_017841.4:c.36+17T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-61430199-T-C
• chr11-61430199-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_017841.4(SDHAF2):​c.36+17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000825 in 1,614,176 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00047 (6 hom.)
• Consequence: SDHAF2 NM_017841.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.472

Genes affected

SDHAF2 (HGNC:26034): (succinate dehydrogenase complex assembly factor 2) This gene encodes a mitochondrial assembly factor needed for the flavination of a succinate dehydrogenase complex subunit (SDHA), which is required for activity of the succinate dehydrogenase complex. Mutations in this gene are associated with paraganglioma. [provided by RefSeq, May 2022]

ENSG00000256591 (HGNC:):

CPSF7 (HGNC:30098): (cleavage and polyadenylation specific factor 7) Cleavage factor Im (CFIm) is one of six factors necessary for correct cleavage and polyadenylation of pre-mRNAs. CFIm is composed of three different subunits of 25, 59, and 68 kDa, and it functions as a heterotetramer, with a dimer of the 25 kDa subunit binding to two of the 59 or 68 kDa subunits. The protein encoded by this gene represents the 59 kDa subunit, which can interact with the splicing factor U2 snRNP Auxiliary Factor (U2AF) 65 to link the splicing and polyadenylation complexes. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 11-61430199-T-C is Benign according to our data. Variant chr11-61430199-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 260943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-61430199-T-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00422 (643/152352) while in subpopulation AFR AF= 0.0143 (596/41592). AF 95% confidence interval is 0.0134. There are 1 homozygotes in gnomad4. There are 314 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 643 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDHAF2	NM_017841.4	c.36+17T>C		intron_variant	Intron 1 of 3	ENST00000301761.7	NP_060311.1
CPSF7	NM_001142565.3	c.-341A>G		upstream_gene_variant		ENST00000439958.8	NP_001136037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDHAF2	ENST00000301761.7	c.36+17T>C		intron_variant	Intron 1 of 3	1	NM_017841.4	ENSP00000301761.3
ENSG00000256591	ENST00000541135.5	c.36+17T>C		intron_variant	Intron 1 of 4	4		ENSP00000443130.1
CPSF7	ENST00000439958.8	c.-341A>G		upstream_gene_variant		1	NM_001142565.3	ENSP00000397203.3

Frequencies

GnomAD3 genomes AF: 0.00423 AC: 644 AN: 152234 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00132 AC: 331 AN: 250546 Hom.: 5 AF XY: 0.000893 AC XY: 121 AN XY: 135532

Gnomad AFR exome AF: 0.0175

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.000983

GnomAD4 exome AF: 0.000471 AC: 688 AN: 1461824 Hom.: 6 Cov.: 31 AF XY: 0.000397 AC XY: 289 AN XY: 727212

Gnomad4 AFR exome AF: 0.0165

Gnomad4 AMR exome AF: 0.00127

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.000960

GnomAD4 genome AF: 0.00422 AC: 643 AN: 152352 Hom.: 1 Cov.: 33 AF XY: 0.00421 AC XY: 314 AN XY: 74498

Gnomad4 AFR AF: 0.0143

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00197 Hom.: 0

Bravo AF: 0.00536

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jun 15, 2017

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary pheochromocytoma-paraganglioma Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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	-0.78
CADD	Benign	4.9
DANN	Benign	0.65

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: rs201389647; hg19: chr11-61197671;