chr15-30371117-G-A

Variant names:

• chr15-30371117-G-A
• rs201185507
• NM_139320.2:c.591C>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_139320.2(CHRFAM7A):​c.591C>T​(p.Ser197Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00558 in 148,658 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0056 (1 hom., cov: 24)
  • Exomes 𝑓: 0.0074 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHRFAM7A NM_139320.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.73

Genes affected

CHRFAM7A (HGNC:15781): (CHRNA7 (exons 5-10) and FAM7A (exons A-E) fusion) The nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. The family member CHRNA7, which is located on chromosome 15 in a region associated with several neuropsychiatric disorders, is partially duplicated and forms a hybrid with a novel gene from the family with sequence similarity 7 (FAM7A). Alternative splicing has been observed, and two variants exist, for this hybrid gene. The N-terminally truncated products predicted by the largest open reading frames for each variant would lack the majority of the neurotransmitter-gated ion-channel ligand binding domain but retain the transmembrane region that forms the ion channel. Although current evidence supports transcription of this hybrid gene, translation of the nicotinic acetylcholine receptor-like protein-encoding open reading frames has not been confirmed. [provided by RefSeq, Jul 2008]

LOC105370751 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-1.73 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRFAM7A	NM_139320.2	c.591C>T	p.Ser197Ser	synonymous_variant	Exon 8 of 10	ENST00000299847.7	NP_647536.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRFAM7A	ENST00000299847.7	c.591C>T	p.Ser197Ser	synonymous_variant	Exon 8 of 10	1	NM_139320.2	ENSP00000299847.3
CHRFAM7A	ENST00000401522.7	c.318C>T	p.Ser106Ser	synonymous_variant	Exon 9 of 11	1		ENSP00000385389.3
CHRFAM7A	ENST00000397827.7	c.318C>T	p.Ser106Ser	synonymous_variant	Exon 7 of 9	5		ENSP00000380927.3
CHRFAM7A	ENST00000692430.1	n.543C>T		non_coding_transcript_exon_variant	Exon 3 of 5

Frequencies

GnomAD3 genomes AF: 0.00558 AC: 829 AN: 148546 Hom.: 1 Cov.: 24

Gnomad AFR AF: 0.00134

Gnomad AMI AF: 0.00444

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.00932

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00147

Gnomad FIN AF: 0.00332

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00898

Gnomad OTH AF: 0.00982

GnomAD3 exomes AF: 0.00529 AC: 1172 AN: 221678 Hom.: 1 AF XY: 0.00545 AC XY: 652 AN XY: 119558

Gnomad AFR exome AF: 0.000995

Gnomad AMR exome AF: 0.00417

Gnomad ASJ exome AF: 0.0122

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00253

Gnomad FIN exome AF: 0.00267

Gnomad NFE exome AF: 0.00787

Gnomad OTH exome AF: 0.00490

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00738 AC: 9919 AN: 1343748 Hom.: 4 Cov.: 26 AF XY: 0.00725 AC XY: 4879 AN XY: 673242

Gnomad4 AFR exome AF: 0.00172

Gnomad4 AMR exome AF: 0.00423

Gnomad4 ASJ exome AF: 0.0121

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.00254

Gnomad4 FIN exome AF: 0.00320

Gnomad4 NFE exome AF: 0.00854

Gnomad4 OTH exome AF: 0.00669

GnomAD4 genome AF: 0.00558 AC: 829 AN: 148658 Hom.: 1 Cov.: 24 AF XY: 0.00483 AC XY: 351 AN XY: 72650

Gnomad4 AFR AF: 0.00134

Gnomad4 AMR AF: 0.00498

Gnomad4 ASJ AF: 0.00932

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00147

Gnomad4 FIN AF: 0.00332

Gnomad4 NFE AF: 0.00898

Gnomad4 OTH AF: 0.00972

Alfa AF: 0.00314 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CHRFAM7A: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.33
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs201185507; hg19: chr15-30663320;