rs151253274

Variant names:

• chr11-22625715-G-A
• rs151253274
• NM_022725.4:c.96C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-22625715-G-A
• chr11-22625715-G-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_022725.4(FANCF):​c.96C>T​(p.Arg32Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00532 in 1,614,116 control chromosomes in the GnomAD database, including 419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R32R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0086 (48 hom., cov: 33)
  • Exomes 𝑓: 0.0050 (371 hom.)
• Consequence: FANCF NM_022725.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.486
• Publications: 5 publications found

Genes affected

FANCF (HGNC:3587): (FA complementation group F) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group F. [provided by RefSeq, Jul 2008]

GAS2 (HGNC:4167): (growth arrest specific 2) The protein encoded by this gene is a caspase-3 substrate that plays a role in regulating microfilament and cell shape changes during apoptosis. It can also modulate cell susceptibility to p53-dependent apoptosis by inhibiting calpain activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2017]

GAS2 Gene-Disease associations (from GenCC):

• hearing loss disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• hearing loss, autosomal recessive 125

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 11-22625715-G-A is Benign according to our data. Variant chr11-22625715-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 261631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.486 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0578 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022725.4. 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
	FANCF	NM_022725.4	MANE Select	c.96C>T	p.Arg32Arg	synonymous	Exon 1 of 1	NP_073562.1	A3KME0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCF	ENST00000327470.6	TSL:6 MANE Select	c.96C>T	p.Arg32Arg	synonymous	Exon 1 of 1	ENSP00000330875.3	Q9NPI8
	GAS2	ENST00000528582.5	TSL:3	c.-119G>A		5_prime_UTR	Exon 1 of 6	ENSP00000432584.1	E9PQ74
	GAS2	ENST00000648096.1		n.207G>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00861 AC: 1310 AN: 152210 Hom.: 49 Cov.: 33

Gnomad AFR AF: 0.00263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0610

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0244

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00819

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000514

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.0198 AC: 4957 AN: 250120 AF XY: 0.0152

Gnomad AFR exome AF: 0.00212

Gnomad AMR exome AF: 0.118

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0266

Gnomad FIN exome AF: 0.00791

Gnomad NFE exome AF: 0.000700

Gnomad OTH exome AF: 0.0129

GnomAD4 exome AF: 0.00497 AC: 7269 AN: 1461788 Hom.: 371 Cov.: 32 AF XY: 0.00434 AC XY: 3159 AN XY: 727208

African (AFR) AF: 0.00111 AC: 37 AN: 33480

American (AMR) AF: 0.111 AC: 4950 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26130

East Asian (EAS) AF: 0.0291 AC: 1157 AN: 39700

South Asian (SAS) AF: 0.000499 AC: 43 AN: 86258

European-Finnish (FIN) AF: 0.00954 AC: 509 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000199 AC: 221 AN: 1112000

Other (OTH) AF: 0.00581 AC: 351 AN: 60388

GnomAD4 genome AF: 0.00861 AC: 1312 AN: 152328 Hom.: 48 Cov.: 33 AF XY: 0.00959 AC XY: 714 AN XY: 74486

African (AFR) AF: 0.00262 AC: 109 AN: 41586

American (AMR) AF: 0.0610 AC: 934 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0244 AC: 126 AN: 5162

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00819 AC: 87 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000514 AC: 35 AN: 68034

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.00249 Hom.: 4

Bravo AF: 0.0131

Asia WGS AF: 0.0130 AC: 45 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Fanconi anemia complementation group F (3)
-	-	2	not provided (2)
-	-	1	FANCF-related disorder (1)
-	-	1	Fanconi anemia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	5.5
DANN	Benign	0.94
PhyloP100		-0.49
PromoterAI		0.0017	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: rs151253274; hg19: chr11-22647261;