rs7178375

Variant names:

• chr15-30923732-C-T
• rs7178375
• NM_014967.5:c.2172+1378C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014967.5(FAN1):​c.2172+1378C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,232 control chromosomes in the GnomAD database, including 3,001 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 0.19 (3001 hom., cov: 33)
• Consequence: FAN1 NM_014967.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351

Genes affected

FAN1 (HGNC:29170): (FANCD2 and FANCI associated nuclease 1) This gene plays a role in DNA interstrand cross-link repair and encodes a protein with 5' flap endonuclease and 5'-3' exonuclease activity. Mutations in this gene cause karyomegalic interstitial nephritis. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Feb 2016]

MTMR10 (HGNC:25999): (myotubularin related protein 10) Predicted to enable phosphatidylinositol-3-phosphatase activity. Predicted to be involved in phosphatidylinositol dephosphorylation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAN1	NM_014967.5	c.2172+1378C>T		intron_variant	Intron 8 of 14	ENST00000362065.9	NP_055782.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAN1	ENST00000362065.9	c.2172+1378C>T		intron_variant	Intron 8 of 14	1	NM_014967.5	ENSP00000354497.4

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28920 AN: 152114 Hom.: 2983 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.190 AC: 28984 AN: 152232 Hom.: 3001 Cov.: 33 AF XY: 0.189 AC XY: 14067 AN XY: 74436

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.202

Alfa AF: 0.165 Hom.: 1037

Bravo AF: 0.199

Asia WGS AF: 0.190 AC: 658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.82

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: rs7178375; hg19: chr15-31215935;