rs17704641

Variant names:

• chr11-61415916-C-T
• rs17704641
• NM_001142565.3:c.939-132G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-61415916-C-T
• chr11-61415916-C-A
• chr11-61415916-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142565.3(CPSF7):​c.939-132G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 846,474 control chromosomes in the GnomAD database, including 7,081 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.096 (915 hom., cov: 32)
  • Exomes 𝑓: 0.12 (6166 hom.)
• Consequence: CPSF7 NM_001142565.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.611
• Publications: 12 publications found

Genes affected

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142565.3. 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
	CPSF7	NM_001142565.3	MANE Select	c.939-132G>A		intron	N/A	NP_001136037.1	Q8N684-2
	CPSF7	NM_024811.4		c.1095-132G>A		intron	N/A	NP_079087.3
	CPSF7	NM_001136040.4		c.966-132G>A		intron	N/A	NP_001129512.1	Q8N684-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPSF7	ENST00000439958.8	TSL:1 MANE Select	c.939-132G>A		intron	N/A	ENSP00000397203.3	Q8N684-2
	CPSF7	ENST00000340437.8	TSL:1	c.1095-132G>A		intron	N/A	ENSP00000345412.4	Q8N684-3
	CPSF7	ENST00000394888.8	TSL:2	c.966-132G>A		intron	N/A	ENSP00000378352.4	Q8N684-1

Frequencies

GnomAD3 genomes AF: 0.0966 AC: 14685 AN: 152072 Hom.: 915 Cov.: 32

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0751

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0154

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.125 AC: 86763 AN: 694284 Hom.: 6166 Cov.: 9 AF XY: 0.127 AC XY: 45693 AN XY: 359514

African (AFR) AF: 0.0214 AC: 374 AN: 17478

American (AMR) AF: 0.0559 AC: 1471 AN: 26300

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 2528 AN: 15928

East Asian (EAS) AF: 0.0166 AC: 583 AN: 35134

South Asian (SAS) AF: 0.150 AC: 8020 AN: 53586

European-Finnish (FIN) AF: 0.162 AC: 7313 AN: 45148

Middle Eastern (MID) AF: 0.117 AC: 453 AN: 3860

European-Non Finnish (NFE) AF: 0.133 AC: 61733 AN: 462524

Other (OTH) AF: 0.125 AC: 4288 AN: 34326

GnomAD4 genome AF: 0.0965 AC: 14685 AN: 152190 Hom.: 915 Cov.: 32 AF XY: 0.0967 AC XY: 7199 AN XY: 74418

African (AFR) AF: 0.0242 AC: 1006 AN: 41526

American (AMR) AF: 0.0750 AC: 1147 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 586 AN: 3470

East Asian (EAS) AF: 0.0154 AC: 80 AN: 5186

South Asian (SAS) AF: 0.132 AC: 639 AN: 4830

European-Finnish (FIN) AF: 0.168 AC: 1776 AN: 10578

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9116 AN: 67992

Other (OTH) AF: 0.0988 AC: 208 AN: 2106

Alfa AF: 0.113 Hom.: 2226

Bravo AF: 0.0856

Asia WGS AF: 0.0680 AC: 238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.23
DANN	Benign	0.41
PhyloP100		-0.61
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: rs17704641; hg19: chr11-61183388;