rs7596205

Variant names:

• chr2-189563467-G-A
• rs7596205
• NM_014585.6:c.1402+117C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-189563467-G-A
• chr2-189563467-G-T

Variant summary

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

The NM_014585.6(SLC40A1):​c.1402+117C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0962 in 842,504 control chromosomes in the GnomAD database, including 4,494 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 0.078 (651 hom., cov: 32)
  • Exomes 𝑓: 0.10 (3843 hom.)
• Consequence: SLC40A1 NM_014585.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.690
• Publications: 5 publications found

Genes affected

SLC40A1 (HGNC:10909): (solute carrier family 40 member 1) The protein encoded by this gene is a cell membrane protein that may be involved in iron export from duodenal epithelial cells. Defects in this gene are a cause of hemochromatosis type 4 (HFE4). [provided by RefSeq, Jul 2008]

SLC40A1 Gene-Disease associations (from GenCC):

• hemochromatosis type 4

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, Genomics England PanelApp, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014585.6. 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
	SLC40A1	NM_014585.6	MANE Select	c.1402+117C>T		intron	N/A	NP_055400.1	Q9NP59

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC40A1	ENST00000261024.7	TSL:1 MANE Select	c.1402+117C>T		intron	N/A	ENSP00000261024.3	Q9NP59
	SLC40A1	ENST00000852923.1		c.1402+117C>T		intron	N/A	ENSP00000522982.1
	SLC40A1	ENST00000852924.1		c.1402+117C>T		intron	N/A	ENSP00000522983.1

Frequencies

GnomAD3 genomes AF: 0.0784 AC: 11913 AN: 151948 Hom.: 645 Cov.: 32

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.0631

Gnomad ASJ AF: 0.0743

Gnomad EAS AF: 0.0190

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.0941

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0810

GnomAD4 exome AF: 0.100 AC: 69124 AN: 690442 Hom.: 3843 AF XY: 0.102 AC XY: 35956 AN XY: 351280

African (AFR) AF: 0.0262 AC: 435 AN: 16576

American (AMR) AF: 0.0548 AC: 986 AN: 18008

Ashkenazi Jewish (ASJ) AF: 0.0712 AC: 1102 AN: 15468

East Asian (EAS) AF: 0.0259 AC: 827 AN: 31904

South Asian (SAS) AF: 0.168 AC: 7114 AN: 42248

European-Finnish (FIN) AF: 0.0949 AC: 3844 AN: 40512

Middle Eastern (MID) AF: 0.0938 AC: 241 AN: 2568

European-Non Finnish (NFE) AF: 0.105 AC: 51479 AN: 489860

Other (OTH) AF: 0.0930 AC: 3096 AN: 33298

GnomAD4 genome AF: 0.0785 AC: 11930 AN: 152062 Hom.: 651 Cov.: 32 AF XY: 0.0791 AC XY: 5877 AN XY: 74344

African (AFR) AF: 0.0294 AC: 1219 AN: 41496

American (AMR) AF: 0.0630 AC: 962 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0743 AC: 258 AN: 3472

East Asian (EAS) AF: 0.0189 AC: 98 AN: 5186

South Asian (SAS) AF: 0.178 AC: 856 AN: 4820

European-Finnish (FIN) AF: 0.0941 AC: 991 AN: 10536

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7225 AN: 67964

Other (OTH) AF: 0.0873 AC: 184 AN: 2108

Alfa AF: 0.0981 Hom.: 1719

Bravo AF: 0.0698

Asia WGS AF: 0.127 AC: 440 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.27
DANN	Benign	0.50
PhyloP100		-0.69
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7596205;

hg19: chr2-190428193;